Showing papers on "Atropine published in 1974"

The properties of muscarinic receptors in mammalian cerebral cortex

Abstract: 1 The reaction of tritiated propylbenzilylcholine mustard ([3H]-PrBCM; N-2′-chloroethyl-N-[2″,3″-3H2] -propyl-2-aminoethylbenzilate) with homogenates of mammalian brain has been studied. 2 The uptake can be divided into an atropine-sensitive component of fixed capacity (380 pmol/g protein in the rat) and an atropine-insensitive part. 3 The atropine-sensitive portion is identified as muscarinic receptor by its insensitivity to nicotinic antagonists and anticholinesterases and its sensitivity to a range of muscarinic antagonists. 4 The uptake of [3H]-PrBCM is also inhibited by muscarinic agonists and there is reasonable quantitative agreement between the affinities of agonists estimated in this way and in intact tissues by physiological responses. 5 The fraction of [3H]-PrBCM uptake inhibited by muscarinic antagonists and agonists is the same. 6 The amount of receptor found in six mammalian species was inversely related to the size of the brain, but the rates of alkylation and the sensitivity to atropine were not dissimilar.

Cholinergic and Adrenergic Release Mechanism for Vasopressin in the Male Rat: A Study with Injections of Neurotransmitters and Blocking Agents into the Third Ventricle

Abstract: The injection into the 3rd ventricle of betha-nechol, carbachol and noradrenaline provoked the release of antidiuretic hormone (ADH) in the hydrated male rat, as indicated by a decrease in urine flow and free-water clearance, with an increased urinary electrolyte concentration, osmolality and conductivity. Atropine completely blocked the bethanechol- and carbachol-induced anti-diuresis, whereas phentolamine and pentolinium did not. On the other hand, the noradrenaline-induced antidiuresis was blocked by phentolamine, but not by atropine or pentolinium. Intraventricular injections of different doses of nicotine did not elicit any release of vasopressin. It is therefore concluded that separate synapses with the neurosecretory cell of both cholinergic muscarinic and α-adrenergic origin exist.

The effects of parasympathetic nerve stimulation on the microcirculation and secretion in the nasal mucosa of the cat.

Abstract: The effects of selective parasympathetic nerve activation on the secretory response and the vascular exchange and capacitance sections in the cat nasal mucosa were studied. The vascular events were investigated by measuring the local disappearance of 125I− and changes in gross pulse rate from 131I-labelled serum albumin as monitored over the nose. A frequency-dependent increase in nasal secretion and local blood content occurred in the range 0.5-12 imp/sec: an increase in disappearance rate was observed at the same time. This indicates that the vascular and secretory responses are activated simultaneously. The secretory responses, but not the vascular events, were shown to be blocked by atropine. Intra-arterial infusion of bradykinin caused an increase in the disappearance rate similar to that seen after parasympathetic nerve stimulation, whereas infusion of arachidonic acid or indomethacin had no effect. The results thus show that the postganglionic parasympathetic mediator of nasal secretion is choliner...

Mechanism of the cardiovascular effects produced by purified scorpion toxin in the rat

Abstract: The effects of a purified toxin fraction of the scorpion Tityus serrulatus were investigated in anesthetized rats. Toxin, in doses of 5 to 20 µg/100 g, produced sinus tachycardia, whereas 40 and 80 µg/100 g evoked sinus bradycardia, sinoatrial and atrioventricular block, ventricular ectopic beats and idioventricular rhythm. Bilateral vagotomy did not prevent the arrhythmias. In vagotomized animals, physostigmine enhanced, hexamethonium decreased and atropine abolished the bradycardiac effect. Propranolol prevented or abolished the sinus tachycardia and changed the ventricular into a sinus rhythm. The pressor effect of toxin was not abolished by hexamethonium, but was significantly decreased by reserpine, guanethidine or phenoxybenzamine in intact rats, and abolished by guanethidine in adrenalectomized animals. It is concluded that: 1) the cardiac arrhythmias are caused by the release of acetylcholine and catecholamines; 2) the bradycardia is due to release of acetylcholine by actions of toxin on vagal ganglia and postganglionic nerve endings in the heart; 3) the sinus tachycardia, the ventricular ectopic beats and the idioventricular rhythm are caused by activation of beta adrenergic receptors in the heart; 4) the hypertension is caused by the release of catecholamines from adrenal glands and postganglionic nerve endings; and 5) the hypotensive effects are due, at least in part, to sinus bradycardia, sinoatrial and atrioventricular blockade.

Breakdown of phosphatidylinositol provoked by muscarinic cholinergic stimulation of rat parotid-gland fragments.

Abstract: When rat parotid fragments that had been labelled with 32P in vivo were exposed to high concentrations of acetylcholine, radioactivity was lost from phosphatidylinositol but not from other phospholipids. Simultaneously the concentration of phosphatidylinositol in the tissue decreased. If previously unlabelled tissue was incubated with 32Pi an increase in incorporation of radioactivity into phosphatidylinositol was observed during this decrease in concentration. The effects of acetylcholine were blocked by atropine, but not by tubocurarine. The response to acetylcholine was rapid, with up to one-third of the tissue's phosphatidylinositol disappearing within 5min. Similar effects were evoked by stimulation with methacholine and by high concentrations of tetramethylammonium ion; these responses were also atropine-sensitive and tubocurarine-insensitive. It is concluded that the event in inositol lipid metabolism that is affected by acetylcholine stimulation is removal of the phosphorylinositol group from the molecule; this is mediated through muscarinic cholinergic receptors. This is followed by a compensatory increase in the rate of synthesis of phosphatidylinositol, which has been described in detail in the past. These observations are compared with those of previous workers and are discussed in relation to the existing hypotheses relating to the significance of stimulus-provoked phosphatidylinositol turnover.

Electrophysiologic effects of atropine on atrioventricular conduction studied by his bundle electrogram

Abstract: The electrophysiologic effects of atropine were studied with His bundle recordings in 14 patients. Administration of atropine, 0.5 mg intravenously, produced a moderate degree of sinus acceleration in all patients (average increase 20 percent over control rate). Atrioventricular (A-V) nodal conduction was enhanced during both sinus rhythm and at various paced atrial rates after administration of atropine. The paced atrial rates at which the A-V nodal Wenckebach phenomenon occurred were significantly higher after administration of the drug than before. Similar effects on retrograde conduction were observed during ventricular pacing. Atropine shortened both the functional and effective refractory periods of the A-V node but appeared to have no direct effect on either His-Purkinje conduction time or refractoriness. However, aberrant ventricular conduction and block within the His-Purkinje system increased during premature atrial stimulation after atropine administration. This was the result of shortening of the functional refractory period of the A-V node by atropine, which produced significantly shorter H1–H2 intervals. The effect of atropine on the electrophysiologic properties of the A-V conducting system was important in interpreting the conversion of a type I gap in A-V conduction to a type II gap.

Cholinergic Modification of Glucose-Induced Biphasic Insulin Release in Vitro

Abstract: An in vitro system for perifusion of rat pancreatic islets has been utilized to define the effects of cholinergic agents on the dynamics of insulin release. In the absence of glucose the effects of either acetylcholine or acetyl-β-methylcholine were minimal at concentrations up to 10−5 mM. In the presence of low glucose concentration (2.4 mM), both of the muscarinic agents produced dose-dependent biphasic insulin release. Under these conditions significant insulin release was observed over both phases at concentrations of the muscarinic agents as low as 10−8 mM. Further, the dose response curves relating muscarinic concentration to the total amount of insulin released in each of the two phases showed lack of parallelism between the curves. Nicotinic acid in concentrations up to 10−5 mM had no effect on insulin release in the presence of 2.4 mM glucose. When the glucose concentration was increased to 16.4 mM, the effects of the muscarinic agents were significantly less than those observed in the presence of 2.4 mM glucose. This held true whether the effect was defined as absolute increment due to the muscarinic agent or as percentage of enhancement. Atropine inhibited insulin release induced by both acetylcholine and by 16.4 mM glucose. These data indicate that cholinergic stimulation can play a significant role in modifying insulin release patterns.

Release of prostaglandin from the rabbit isolated heart following vagal nerve stimulation or acetylcholine infusion

Abstract: 1 Rabbit hearts were perfused by the Langendorff technique. The lipid fraction in the perfusate from the heart was isolated and analysed for prostaglandins by thin layer chromatography and quantitative assay on the rat isolated stomach strip.2 Infusion of acetylcholine at a rate of 8 mug/min significantly increased the outflow of prostaglandins from the heart, from 1.8 to 6.2 ng/minute.3 Addition of atropine (1 mug/ml) to the perfusing medium completely abolished not only the mechanical response but also the increase in outflow of prostaglandins caused by infusion of acetylcholine.4 Bilateral stimulation of the parasympathetic nerves to the heart at 5 Hz also significantly increased the outflow of prostaglandins from the organ from 5.2 to 8.3 ng/minute.5 Both prostaglandin E(1) and E(2) were isolated from the lipid fraction of the perfusate.6 The role of prostaglandins in relation to autonomic neurotransmission in the heart is discussed.

Guanosine cyclic 3',5'-monophosphate and guanylate cyclase activity in guinea pig lung: effects of acetylcholine and cholinesterase inhibitors.

Abstract: The effects of acetylcholine, other neurotransmitters, and hormones on the guanosine cyclic 39, 59-monophosphate and adenosine cyclic 39, 59-monophosphate contents of guinea pig lung were investigated. When lung slices were incubated in the presence of 0.1 mM physostigmine and 1 mM theophylline (which themselves had little effect), the addition of acetylcholine produced a prompt rise in cyclic GMP concentration, which reached a maximum (about 250% of basal) in 1-3 min and began to decline by 6 min, approaching control levels in 12 min. When measured at 2 min the effect of 0.1 µM acetylcholine was negligible, and that of 1 µM was essentially maximal. Acetylcholine also increased the cyclic AMP content of lung slices 2-3-fold in 2 min. The effects on both nucleotides were prevented by 0.5 mM atropine. Prostaglandins E1, E2, A2 and F2α (2 µM), 1 µM isoproterenol, and 0.1 mM serotonin had no effect on basal cyclic GMP concentration or on the increment produced by acetylcholine. The cyclic AMP content of lung slices was markedly increased by exposure (for 2 min) to prostaglandin E1, isoproterenol, or epinephrine. The effect of epinephrine was prevented by propranolol and unaffected by phentolamine. Neither of the adrenergic blocking agents alone or in combination with epinephrine significantly affected cyclic GMP levels. Guanylate cyclase activity assayed in whole homogenates of lung was not demonstrably affected by acetylcholine or other cholinergic agents. It was significantly increased by 1 mM physostigmine (alone or in the presence of acetylcholine) but not by other inhibitors of cholinesterase (neostigmine or edrophonium). This effect of physostigmine was not prevented by atropine.

Adverse effect of atropine during myocardial infarction. Enchancement of ischemia following intravenously administered atropine.

Abstract: Intravenously administered atropine sulfate is commonly used for the control of bradycardias during myocardial infarction. There is increasing evidence that this may not be beneficial to the patient and that serious arrhythmias may be produced. Atropine has also been demonstrated to increase the area of ischemia during myocardial infarction in dogs, but this has not been well documented in humans. It is suggested that atropine be used cautiously during myocardial infarction, and only when the hemodynamic situation clearly warrants its use or when a serious cardiac arrhythmia exists. ( JAMA 228:1414-1416, 1974)

Formation of a factor increasing vascular permeability during electrical stimulation of the saphenous nerve in rats.

Abstract: 1 Increased vascular permeability following electric antidromic stimulation of the rat saphenous nerve was observed in the skin area supplied by the nerve, confirming previous results by other authors. 2 The phenomenon was not affected by pretreatment of the rats with diphenhydramine, burimamide or their combination; atropine, methysergide, methysergide plus diphenhydramine, carboxypeptidase B, acetylsalicylic acid, indomethacin or methiazinic acid. It was partially reduced by previous injection of cellulose-sulphate, a kininogen-depleting agent. 3 Perfusates from the subcutaneous tissue of the paw area supplied by the saphenous nerve contained permeability increasing activity as shown by intradermal tests in other rats. This activity was present in perfusates collected during nerve stimulation but not in those collected before stimulation. It was not destroyed by heating to 100° C, or by α-chymotrypsin or trypsin. 4 Bradykinin-like activity may appear later in the perfusates, depending on the intensity of the stimuli. 5 It is concluded that following electrical antidromic stimulation of the saphenous nerve a permeability increasing factor is released, possibly from nerves. It is dialysable and can be distinguished from acetylcholine, histamine, 5-hydroxytryptamine, plasma kinins, substance P, prostaglandins and high molecular weight proteins. The increased vascular permeability induced by this factor leads to plasma exudation and activation of the kinin system.

Bradykinin-induced coronary chemoreflex in the dog.

Abstract: The injection of 1.0 μg of bradykinin into the left coronary artery of anaesthetized dogs produces a simultaneous decrease in blood pressure and heart rate and also a less pronounced decrease in respiratory rate and amplitude. These effects are quite similar, although less intense, to those evoked by equivalent doses of veratrine. Moreover, there is no tachyphylaxis if the interval between injections is kept around 10 min. The cardiovascular changes are proportional to the dose of bradykinin up to 4.0 μg; with increasing doses only the hypotensive action is increased. Smaller doses of bradykinin are only effective in the presence of the bradykinin-potentiating-factor, BPF10 (1.0 mg/kg). The bradycardia, but not the hypotension, is potentiated by neostigmine (0.5 mg), and abolished by atropine (1.0 mg/kg). Cervical bilateral vagotomy abolishes the bradycardia and reduces the hypotension elicited by intracoronary bradykinin. When injected into the right atrium bradykinin causes hypotension and an increase in heart rate, even in the presence of BPF10. It is concluded that bradykinin induces a coronary chemoreflex when injected into the coronary artery of the dog.

Pharmacological observations on the hypotensive action of extracts of teleost fish urophyses (urotensin i) in the rat

Abstract: 1 Intravenous injections of urotensin I regularly caused a long-lasting, dose-related, lowering of blood pressure and an increase in heart rate in conscious rats, or a reduction in perfusion pressure in the isolated hind limb of the rat.2 After subcutaneous administration, the hypotensive effect of urotensin I was greater in extent and in duration (> 24 hours).3 Anaesthesia with ether, chloralose, pentobarbitone and thiobarbitone caused a decrease in blood pressure and only slightly diminished the hypotensive effect of urotensin.4 Mecamylamine, hexamethonium, atropine, phenoxybenzamine, propranolol and diphenhydramine did not alter the effect of urotensin in conscious rats or in the isolated hind limb, although the effects of the respective agonists, i.e. nicotine, acetylcholine, noradrenaline, isoprenaline and histamine were inhibited.5 In conscious rats, pressor effects of adrenaline, noradrenaline, nicotine and angiotensin II, and depressor effects of acetylcholine and bradykinin, were decreased or inhibited, whereas the hypotensive effect of phenoxybenzamine was potentiated by previous administration of urotensin I. Carotid occlusion reflex was partially inhibited by lower doses of urotensin and abolished by higher doses in rats lightly anaesthetized with chloralose. Urotensin elicited postural hypotension in rats anaesthetized with pentobarbitone.6 The increase in heart rate produced by urotensin was not affected by phenoxybenzamine, but was abolished by propranolol or ganglion blocking agents (mecamylamine or hexamethonium).7 It is concluded that urotensin elicits hypotension in the rat by a direct dilatory action on the resistance vessels causing a simultaneous reflex tachycardia.

Antiacetylcholine drugs: chemistry, stereochemistry, and pharmacology.

Abstract: Publisher Summary This chapter discusses the chemistry, stereochemistry, and pharmacology of antiacetylcholine drugs Acetylcholine and certain other esters and ethers of choline have marked effects on the cardiovascular system with low doses causing reductions in blood pressure and higher doses reductions in heart rate These effects are abolished by atropine but not influenced by section of the vagus and so are assumed to be peripheral in origin Larger doses of acetylcholine given to atropinized animals cause increases in blood pressure The actions of acetylcholine and related agonist drugs at the postganglionic parasympathetic endings are muscarinic, whereas agonist actions at autonomic ganglia and the skeletal neuromuscular junction are nicotinic Similarly, there are antagonist drugs, which more or less specifically block the actions of acetylcholine at these different sites Unless accurate and reproducible pharmacological testing procedures are chosen and evaluated thoroughly, attempts to interpret pharmacological results in terms of mechanism of drug action are of little value

Investigations on the effects of diazepam in acute experimental intoxication with fluostigmine.

Abstract: The therapeutic effectiveness of diazepam in organophosphate intoxication was studied. It was demonstrated that this drug as an adjunct to a mixture of atropine and obidoxime raised the LD50 of fluostigmine in rats to a value about 80 times that in untreated rats. Diazepam alone had no therapeutic effect in these conditions. Diazepam quickly abolished the convulsive electrical activity of the rabbit cortex induced by fluostigmine, normalized the fluostigmine increased amplitude of indirectly elicited twitches of the skeletal muscle of the rat and arrested the disintegration of the muscle action potential observed in these cases. Diazepam had no influence on the block of tetany or on desynchronization of the basal bioelectrical activity of the cortex due to fluostigmine.

Atropine toxicity in a neonate

Abstract: SUMMARY This case report is of a child who suffered a toxic reaction to an overdose of atropinc and then of physostigmine. The central anti-cholinergic toxicity of the atropine was initially reversed by physostigmine resulting in an incipient muscarinic crisis. This crisis was averted by glycopyrrolate, thereby allowing completion of the reversal with physostigmine.

A central vasodepressor effect of Dyflos.

Abstract: 1 Cats were anaesthetized with pentobarbitone sodium and atropinized peripherally by intravenous injection of atropine methyl nitrate; the effect was examined of topical bilateral application of dyflos to the ventral surface of the medulla oblongata at a region lateral to the pyramids and caudal to the trapezoid bodies. Dyflos was applied by means of perspex rings; the volume of fluid placed in each ring was 10 μl. 2 The topical application of dyflos (1-20 mg/ml) produced a fall in arterial blood pressure without changes in heart rate and, in experiments without artificial ventilation, tachypnoea with dissociation of thoracic and abdominal respiration. 3 Atropine methyl nitrate (50 mg/ml) applied topically in the same way as dyflos, prevented or abolished its vasodepressor effect. 4 The two reactivators of acetylcholinesterase, obidoxime (100-200 mg/ml) and pralidoxime mesylate (100-200 mg/ml), applied topically in the same way as dyflos, abolished its vasodepressor effect. The reactivator compound 30 (100 mg/ml), also a pyridinium aldoxime, did not have this effect. 5 Obidoxime and pralidoxime mesylate also reversed the vasodepression produced by carbachol applied to the ventral surface of the brain stem but not the vasodepression produced by glycine similarly applied. 6 The problem is discussed as to whether the reversal of the dyflos and carbachol-induced vasodepression by obidoxime and pralidoxime is due to acetylcholinesterase reactivation by dephosphorylation and decarbamylation respectively, to a central atropine-like action of these compounds or to a combination of both.

Atropine-resistant effects of the muscarinic agonists McN-A-343 and AHR 602 on cardiac performance and the release of noradrenaline from sympathetic nerves of the perfused rabbit heart.

Abstract: 1 The effects of 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343) and N-benzyl-3-pyrrolidyl acetate methobromide (AHR 602) on cardiac performance and noradrenaline release from terminal sympathetic fibres were measured in isolated perfused hearts of rabbits. 2 In the presence of sufficient atropine to block muscarinic receptors, high concentrations of McN-A-343 and AHR 602 caused no cardiac stimulation and there was no increase in the resting output of noradrenaline into the perfusates. 3 McN-A-343 and AHR 602 increased both the mechanical responses and the transmitter overflow evoked by electrical stimulation of the sympathetic nerves (SNS) but inhibited both parameters during perfusion with 1,1-dimethyl-4-phenylpiperazinium (DMPP). The effects were atropine-resistant and qualitatively similar to those seen with cocaine. Hexamethonium inhibited DMPP, but affected neither SNS per se nor the facilitatory effects of McN-A-343 and AHR 602 on SNS. 4 McN-A-343, cocaine and desipramine (but not AHR 602 or hexamethonium) blocked the net cardiac noradrenaline uptake and increased the positive chronotropic effect of noradrenaline. 5 Prior perfusion with concentrations of cocaine and desipramine sufficient to block uptake reduced or abolished the facilitatory effects of both McN-A-343 and AHR 602 on SNS. 6 Cocaine, McN-A-343 and AHR 602 displayed local anaesthetic properties on the guinea-pig wheal and frog nerve plexus tests, and their relative potencies in this respect were similar to those for inhibition of DMPP-evoked transmitter overflow. Hexamethonium did not produce local anaesthesia. 7 The results indicate that the facilitated release of noradrenaline after SNS and the inhibition of release after DMPP produced by McN-A-343 and AHR 602 are the result of their combined local anaesthetic action and inhibition of amine uptake.

Alteration of ethanol-induced cns depression: Ineffectiveness of drugs that modify cholinergic transmission

Abstract: Rats trained to perform in a discriminated lever-press avoidance situation were given ethanol orally to depress their performance. In an attempt to modify the ethanol-induced depression with drugs which would reverse or enhance reported effects of ethanol in reducing free cerebral acetylcholine, parenteral atropine, intraventricular hemicholinium, and intraventricular acetylcholine were given during ethanol intoxication. None of the drugs significantly altered the ethanol-induced behavioral depression, suggesting that the reported reduction in free acetylcholine during ethanol intoxication may merely reflect decreased neuronal activity, rather than being an important causative factor in ethanol-induced CNS depression.

Neurochemical bases of defensive behavior in animals.

Abstract: This paper presents a literature review and the author's own investigations devoted to identifying the morphological organization of different subcortical structures and neurochemical processes involved in the (regulation of defensive behavior. The effects of intrahypothalamic injections of two cholinomimetic substances, carbachol and d-tubocurarine, on rage and fear reactions were explored. Also the investigations were carried out with intrahypothalamic injections of anticholinergic substances, atropine and betamon or hexamethonium, which block selectively muscarinic and nicotinic receptors. The results indicate that carbachol injected into the hypothalamus after blocking the muscarinic receptors with atropine fails to elicit any defensive response; whereas carbachol injection administrated after nicotinic receptors had been blocked by betamon or hexamethonium induces full aggressive behavior. This indicated that carbachol acts, on the hypothalamic level, through the muscarinic receptors. The mechanism of d-tubocurarine action seems to be more complex because this compound induces fear response after either the muscarinic or the nicotinic receptors have been blocked. A possible mechanism based on chemically differentiated neuronal circuits at the hypothalamic level for two different defensive drives, fear and rage, is presented.

Parasympathetic nervous control of airway smooth muscle.

Abstract: Airway smooth muscle responses to many inhaled substances have been shown to involve the parasympathetic nervous system. The purpose of this communication is to discuss this nervous regulation of airways, particularly as it relates to inhaled materials. Both parasympathetic and sympathetic nerves innervate the airways, but only the parasympathetic system will be dealt with in the present discussion. The parasympathetic efferent nerve supply to the airways is via the vagus nerves. Vagal preganglionic fibers enter the lungs and terminate in ganglia located within the airways themselves.' Studies with acetylcholinesterase stains indicate a dense cholinergic innervation of bronchi in all species studied.2 The airways of dogs,3 cats,4 rabbits,6 and healthy humans are tonically constricted, and this tone is maintained by vagal efferent nervous activity. Thus, cutting the vagus nerves in animals or administration of atropine sulphate (a drug which blocks postganglionic cholinergic pathways) in healthy subjects results in dilation of the airways. When the vagus nerves are stimulated, constriction occurs from the trachea to large bronchioles; maximum constriction occurs in bronchi of intermediate size.' Since these airways are the sites of most of the resistance to airflow,* reflex bronchoconstriction causes marked changes in airflow resistance.@ Terminal bronchioles and alveolar ducts are unaffected by reflex bronchoconstriction,J. so lung compliance is usually unchanged unless bronchoconstriction is severe.@ These findings are confirmed by histochemical studies which demonstrate the presence of acetylcholinesterase in bronchi and bronchioles but not in alveolar ducts or alveoli.? When one lung is removed from a dog and reimplanted, it is completely denervated and the airway smooth muscle does not respond to vagal stimulation.lo However, vagal reinnervation of bronchial smooth muscle occurs within three months. This rapid reinnervation can be explained by the fact that parasympathetic ganglia are located within the airways themselves. Thus, within the reimplanted lung, preganglionic fibers degenerate, but ganglia and undivided postganglionic fibers do not. Thus, regenerating preganglionic axons must reach ganglia that are located only a few centimeters from the line of division, so reinnervation occurs rapidly. This rapid reinnervation is one reason why surgical pulmonary vagal denervation is not likely to be an effective procedure. airway irritation,\"-13 and histamine 1 ' 9 l5 constrict the airways reflexly by stimulating Various stimuli including hypercapnia, hypoxemia, hyp~tension,~.

The rabbit rectococcygeus: A ganglion-free, parasympathetically innervated preparation

Abstract: 1 Isolated, desheathed preparations of the rabbit rectococcygeus muscle were relatively insensitive to spasmogens other than muscarinic drugs. Transmural stimulation with 1-50 pulses (0.2-0.4 ms at 10 Hz) elicited graded twitches which were abolished by tetrodotoxin and were therefore neurogenic; longer pulses sometimes triggered tetrodotoxin-resistant myogenic contractions.2 Twitches elicited by 0.2-0.4 ms pulses were due to post-ganglionic excitation because they were not reduced by hexamethonium, pentolinium or dimethyltubocurarine, or by ganglion-paralyzing concentrations of nicotine.3 The acetyl- and butyryl-cholinesterase activities of the rectococcygeus were determined manometrically and could be selectively inhibited by BW 284C51 (1:5-bis-(4-allyl-dimethylammonium-phenyl)-pentan-3-one dibromide) and iso-OMPA (tetramonoisopropylpyrophosphortetramide), respectively. Single-pulse twitches were greatly potentiated in amplitude and duration only when both cholinesterases were inhibited.4 The preparations could not be made to contract by nicotine (2.1-21 muM) even after cholinesterase inhibition, suggesting an absence of ganglion-cells; with nicotine (105-210 muM) small, atropine-susceptible responses were elicited, which were non-ganglionic because they were not reduced by tetrodotoxin.5 Rectococcygeus preparations that had been treated with physostigmine released acetylcholine into the bath fluid on electrical stimulation.6 The motor transmission was paralyzed by botulinum toxin (Type A) and abolished by atropine; the block of muscarinic receptors by atropine was effective against both endogenous and exogenous acetylcholine.7 Inhibitory adrenoceptors and scanty motor alpha-adrenoceptors were detected in the smooth muscle.8 Strong inhibitions of motor transmission and of rhythmic activity were produced by noradrenaline (but not by tyramine), by isoprenaline, and, after phentolamine, also by adrenaline and phenylephrine. These inhibitions were only slightly reduced by propranolol and rather more by pindolol.9 Experiments on preparations retaining their extrinsic nerve supply suggest an absence of ganglionic relays in the last 1-2 cm of the motor nerve pathway to this muscle.10 Some contrasting properties of the adjacent caudo-anal muscle, including the poor motor responses to transmural stimulation, are described.

Effects of the muscarinic agonist McN-A-343 on the release by sympathetic nerve stimulation of (3H)-noradrenaline from rabbit isolated ear arteries and guinea-pig atria.

Abstract: 1 McN-A-343 (4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride) in concentrations of 10-5 and 10-4 M inhibits the stimulation-induced efflux of radioactivity from segments of rabbit ear artery that have previously been incubated with (-)-[3H]-noradrenaline, and also decreases the contractile response. 2 The inhibitory effects of McN-A-343 (10-5 M) on the efflux of radioactivity and the contractions induced by low frequencies of stimulation (2 and 5 Hz) are reversed by atropine, but atropine does not modify these effects with high frequencies of stimulation (20 and 50 Hz). 3 McN-A-343 (10-4 M) enhances the stimulation-induced efflux of radioactivity from guinea-pig atria that have previously been incubated with (-)-[3H]-noradrenaline, and prolongs the positive inotropic response. These effects are not modified by atropine. 4 It is concluded that McN-A-343 has different effects on adrenergic transmitter release in the two tissues. In the artery, it acts as an agonist on muscarinic receptors of adrenergic terminals to inhibit transmitter release at low frequencies of stimulation. In the atria it enhances transmitter efflux from the tissue, largely by inhibiting re-uptake.