Showing papers in "Canadian Journal of Physiology and Pharmacology in 1974"
TL;DR: Microiontophoretically applied adenine nucleotides depressed the firing of corticospinal and other unidentified cerebral cortical neurones and Guanineucleotides shared this depressant activity, although they were less potent.
Abstract: Microiontophoretically applied adenine nucleotides depressed the firing of corticospinal and other unidentified cerebral cortical neurones. Adenosine 3′,5′-cyclic monophosphate was less potent than...
151 citations
TL;DR: It is suggested that morphine may produce analgesia, at least in part, by a direct action on a specific morphine receptor in the spinal cord.
Abstract: Morphine, applied by microiontophoresis to functionally identified dorsal horn neurones in segments L5–L7 of cats (chloralose anaesthetized, decerebrated or high spinal), produced primarily a depre...
146 citations
TL;DR: Pure Substance P was applied from 7 mM solutions by microiontophoresis to cuneate neurones in cats under barbiturate or inhalation anesthesia and it was concluded that Substance P is unlikely to be the quickly acting transmitter released by primary...
Abstract: Pure Substance P was applied from 7 mM solutions by microiontophoresis to cuneate neurones in cats under barbiturate or inhalation anesthesia. The predominant effect was a slow excitation, beginning after a delay of 10–30 s, reaching a peak some 30 s later, and decreasing only gradually after the end of the application, over 1 min or even longer. It was observed with about half of all the units tested (especially those that were spontaneously active), in all experiments, with several different electrodes, and Substance P obtained from two different sources; and therefore can be considered to reflect a genuine strong but slow depolarizing action. Larger doses of Substance P depressed firing, especially when evoked by glutamate, and, in one experiment, several units showed a mainly depressant effect. This may be explained by a similar slow mechanism of depolarization but with inactivation being predominant. It is concluded that Substance P is unlikely to be the quickly acting transmitter released by primary...
127 citations
TL;DR: The nerve-blocking potencies of anesthetics, alcohols, tranquilizers, antidepressants, anticonvulsants, barbiturates, and narcotics were obtained on the rat phrenic nerve and the sciatic nerves of the frog and the rat.
Abstract: (1) The nerve-blocking potencies of anesthetics, alcohols, tranquilizers, antidepressants, anticonvulsants, barbiturates, and narcotics were obtained on the rat phrenic nerve and the sciatic nerves of the frog and the rat. Skou's second method for equilibrium blockade was used, and complete dose–response curves were obtained on the height of the compound action potential.(2) Uncharged drugs (alcohols, urethane) and acidic drugs (barbiturates, diphenylhydantoin) caused half blockade of the phrenic nerve (11 μm diameter fibers) at concentrations about 25–35% of those causing half blockade of sciatic nerve (16 μm fibers).(3) Tertiary amines (procaine, spirosuccinimide enantiomers, chlorpromazine, haloperidol, trifluperidol, methadone, and naloxone) produced half blockade of the phrenic nerve at concentrations about 10% of those producing half blockade of the sciatic nerve. Frog and rat sciatic C50% block values (i.e. the drug concentration that reduced the compound action potential by 50%) were the same.(4) ...
81 citations
TL;DR: During brief periods of hypoxia caused by the inhalation of pure nitrogen, reversible increases in extracellular potassium activity (aK) were detected in the guinea-pig cortex with K+-selective microelectrodes, associated with an increased negativity of the potential recorded between the reference electrode and ground.
Abstract: During brief periods of hypoxia caused by the inhalation of pure nitrogen, reversible increases in extracellular potassium activity (aK) were detected in the guinea-pig cortex with K+-selective mic
74 citations
TL;DR: Microiontophoretic application of acetylcholine to neurons in the CA1 pyramidal and dentate granule layers of the rabbit hippocampus revealed differences in the number of cells excited and the nature of the excitation in the two populations of neurons.
Abstract: Microiontophoretic application of acetylcholine to neurons in the CA1 pyramidal and dentate granule layers of the rabbit hippocampus revealed differences both in the number of cells excited and the nature of the excitation in the two populations of neurons. A smaller percentage (35.7%) of CA1 pyramidal neurons were found to be excited by acetylcholine, compared with the percentage (92.3%) of dentate granule cells excited. Excitation of CA1 pyramidal cells was slow in onset and antagonized by atropine. Excitation of dentate granule cells was rapid in onset and atropine did not specifically antagonize the action of acetylcholine on these cells.
65 citations
TL;DR: K+-selective microelectrodes were used to measure extracellular K+ activity in the neuraxis of cats under Dial and found that there is a cumulative, maintained rise in aK during repetitive stimulation at rates > 0.5 s−1, and definite changes can be recorded even with single pulses.
Abstract: K+-selective microelectrodes were used to measure extracellular K+ activity (aK) in the neuraxis of cats under Dial. In resting conditions, aK is stable (in range 2.0–3.0 mM) but may vary systemati...
64 citations
TL;DR: There is a decrease in the energy available to tissues during severe hemorrhagic shock, which could be due to decreased biosynthesis, to continuing or increased utilization of the nucleotides, or to both.
Abstract: Hemorrhagic shock was produced in conscious rats by cannulating the subclavian artery and bleeding the animals to a mean arterial pressure of 40 mm Hg which was maintained for 1 (early shock) or 2 h (late shock). Analysis of tissues showed that there was a significant decrease in ATP and ADP levels in liver and kidney in early and late shock. Associated with the decrease in ATP and ADP levels were increases in AMP and P1 levels. In contrast to the above organs, adenine nucleotides and creatine phosphate levels of skeletal muscle did not decrease in early shock but a significant reduction of these compounds was observed in late shock. The decrease in ATP content was greater in liver and kidney than in skeletal muscle. The present experiments indicate that there is a decrease in the energy available to tissues during severe hemorrhagic shock. This could be due to decreased biosynthesis, to continuing or increased utilization of the nucleotides, or to both.
63 citations
TL;DR: Even at concentrations found in blood after smoking one marihuana cigarette there was a slight inhibition of the Na+–K+-ATPase, which may be due to a specific binding or to a general action of the THC on membranes.
Abstract: The effect of Δ1-trans-tetrahydrocannabinol (THC) on ATPase activities of a microsomal fraction from rat ileum was measured. A concentration of 10−5 M completely abolished the stimulation due to so...
61 citations
TL;DR: Platelet–surface interaction was studied using activated charcoal granules (AC), cellulose nitrate coated, activated charcoal Granules (CAC), albumin – cellulose Nitrate coated ( albumin), and activated charcoalgranules(CAC) to study the interaction between platelet-surface interaction and charcoal content.
Abstract: Platelet–surface interaction was studied using activated charcoal granules (AC), cellulose nitrate coated, activated charcoal granules (CAC), albumin – cellulose nitrate coated, activated charcoal granules (ACAC), and benzokonium – heparin – cellulose nitrate coated, activated charcoal granules (BHCAC). In studies where blood from dogs was recirculated through shunts, each containing 300 g of one of the above systems, it was found that both AC and CAC lowered the systemic blood platelet levels after 2 h of hemoperfusion. In hemoperfusion across these two systems, there was also an increase in the adhesiveness of platelets. In the case of ACAC and BHCAC, hemoperfusion for 2 h did not result in any significant decrease in the systemic blood platelet levels, nor was there an increase in the adhesiveness of platelets perfused across these two systems. Scanning electron microscopic studies were carried out with the CAC and ACAC systems before and after contact with blood. There was marked platelet and fibrin d...
61 citations
TL;DR: It was shown that GABA was bound preferentially to particles of cerebral cortex whereas glycine "binding" occurred preferentialially to those of spinal cord.
Abstract: The "binding" activities of 3H-γ-aminobutyric acid (3H-GABA) and 14C-glycine in synaptosome-enriched factions of rat cerebral cortex and spinal cord have been compared in an isosmotic sucrose medium (containing 32 mM NaCl) over a wide range of concentrations using differential centrifugation and a double-isotope method. It was shown that GABA was bound preferentially to particles of cerebral cortex whereas glycine "binding" occurred preferentially to those of spinal cord. At equimolar concentrations of 3H-GABA and 14C-glycine in the medium (0.8 × 10−7 M – 0.8 × 10−4 M) the order of potency of "binding" was as follows: GABA, cortex > GABA, cord glycine, cord > glycine, cortex. Ratios of GABA/glycine were always much greater than 1.0 for cerebral cortex when these amino acids were present in the medium at 10 −7–10−4 M, whereas these ratios were about 1.0 for spinal cord at all concentrations of the amino acids that were used. The "maximal binding capacity" (Bmax) for GABA, at 0 °C, was estimated to be about...
TL;DR: Dogs treated with androgen or methyltestosterone had a significantly greater heart rate than animals treated with vehicle, however, mean arterial pressures were similar in the two groups.
Abstract: Impairment of testosterone metabolism or excretion has been found in some patients with essential hypertension (Nowacynski et al. Can. J. Biochem. (1968), 46, 1031–1038). The effects of testosteron...
TL;DR: Bile flow was varied by use of bile acid infusions, in order to determine whether the biliary secretory maximum or Tm is indeed constant or whether it varies with flow.
Abstract: Of the processes involved in the handling of a bilirubin load, the biliary secretory maximum or Tm for bilirubin has been regarded as rate limiting, and as a characteristic of liver function. In the present study, bile flow was varied by use of bile acid infusions, in order to determine whether the Tm is indeed constant or whether it varies with flow. Anesthetized dogs, with bile flow stabilized by cholinergic blockade, were studied during taurocholate infusions. In these animals the ductular component of flow is relatively inhibited and the bile flow rate increases approximately in proportion to the rate of excretion of taurocholate. The maximal biliary excretion rate of bilirubin was found to increase linearly with flow and taurocholate excretion, in a significant fashion, but, in contrast to the relation between taurocholate excretion and flow, a significantly large intercept remained on linear extrapolation towards zero flow. The basis for the large intercept is a great increase in the bilirubin conce...
TL;DR: The action of angiotensin II and of several analogues, including antagonists, has been studied on isolated perfused rabbit hearts and changes of transmembrane potential have been recorded from atrial and ventricular fibers with floating microelectrodes.
Abstract: The action of angiotensin II (ATII) and of several analogues, including antagonists, has been studied on isolated perfused rabbit hearts. Changes of transmembrane potential have been recorded from ...
TL;DR: The hypothesis that the subfornical organ is a receptor site for angiotensin-II is supported but it is suggested that this may not be the only site of receptors.
Abstract: The effect of electrolytic lesions of the subfornical organ on water intake induced by the continuous infusion of angiotensin-II through a chronic jugular cannula was studied. Lesions of the subfornical organ significantly reduced but did not abolish the elicited drinking. These results support the hypothesis that the subfornical organ is a receptor site for angiotensin-II but also suggest that this may not be the only site of receptors.
TL;DR: It is concluded that Ca2+ may cause a physiological kind of allosteric antagonism of the drug-blocked Na+ channel, or...
Abstract: This study shows that Ca2+ reversed the nerve-blocking actions of procaine, lidocaine, procainamide, imipramine, chlorpromazine, tetrodotoxin, hexanol, heptanol, benzyl alcohol, thymol, sodium barb...
TL;DR: Experiments with White Carneau pigeons have established that the ease of metabolism of polychlorinated biphenyls (PCBs) composing Aroclor 1254® is determined principally by chlorine substitution patterns rather than degree of chlorination.
Abstract: Experiments with White Carneau pigeons have established that the ease of metabolism of polychlorinated biphenyls (PCBs) composing Aroclor 1254® is determined principally by chlorine substitution pa...
TL;DR: Aspartic acid was replaced in position 1 of angiotensin II (ATII) with several amino acids, to assess the possible influence of the N-terminal amino acid for the intrinsic activity, affinity, and the metabolic degradation of agonist analogues of ATII.
Abstract: Aspartic acid was replaced in position 1 of angiotensin II (ATII) with several amino acids, to assess the possible influence of the N-terminal amino acid for (a) the intrinsic activity, (b) the affinity, and (c) the metabolic degradation of agonist analogues of ATII. Some of the substitutions in position 1 were used in combination with replacement of Phe by Gly or Leu in position 8, to obtain the corresponding antagonist.The compounds were tested in vivo (rat blood pressure) and in two in vitro preparations (rat stomach and rabbit aorta strips). The oil immersion technique, described by Kalsner and Nickerson (1968) (Can. J. Physiol. Pharmacol. 46, 719–730), was used to study the disposition of the peptides by vascular smooth muscles (rabbit aorta strips). Degradation of the peptides by purified aminopeptidases was evaluated in vitro by measuring the fragments on paper chromatography. Potency of antagonists was estimated in vivo (ID50) and in vitro (pA2 values): duration of action was established by infusi...
TL;DR: The data presented are consistent with the hypothesis that the two principal sensory contributions to the bradycardia of immersion are a cessation of the movements of the lungs and rib cage and a change in neural activity in receptors located in the face.
Abstract: Three harbor seals were immersed in five different water temperatures ranging from 7 to 37 °C. Unlike the response in men, the bradycardia observed during immersion was not influenced by water temperature. When the faces of four seals were rendered insensible by neurotomy and local anesthetic, the bradycardia during immersion followed the same time course as that observed during periods of forced apnea while the seals were in air. In two seals with insensible faces, which were forcefully respired during immersion, the heart rate did not drop from the rate observed before immersion. The data presented are consistent with the hypothesis that the two principal sensory contributions to the bradycardia of immersion are: (1) a cessation of the movements of the lungs and rib cage; (2) a change in neural activity in receptors located in the face.
TL;DR: The rate of appearance of glucose (Ra) was estimated in a non-steady state caused by the infusion of glucose or glucagon (increase of hepatic glucose output) in unanesthe...
Abstract: The rate of appearance of glucose (Ra) was estimated in a non-steady state caused by the infusion of glucose (exogenous increase of Ra) or glucagon (increase of hepatic glucose output) in unanesthe
TL;DR: Bile acid and phospholipid phosphorous concentration and percentage solids increased after bile acid administration in all three species; however, species differences in bilirubin concentration were observed and a marked decrease was detected in rabbit and dog bile but it markedly increased in rat bile.
Abstract: Relatively similar concentrations of the inorganic ions were detected in rat, rabbit, and dog bile; however, dog bile had a higher concentration of protein, cholesterol, phospholipid phosphorous, a...
TL;DR: The effects of intermittent light stimulation on chickens genetically predisposed to generalized convulsions are described, suggesting decreased electrical activity similar to the postictal depression seen in the EEG of human epileptics.
Abstract: The effects of intermittent light stimulation on chickens genetically predisposed to generalized convulsions are described. Epileptic chickens (homozygous recessive) convulse when exposed to intermittent light stimulation at 10–25 flashes per second, whereas normal (homozygous dominant) and carrier (heterozygous) hatch mates are not affected. The resting electroencephalogram (EEG) of epileptic chickens is markedly different from that of their nonconvulsive hatch mates, being characterized by high-amplitude slow waves with periodic spikes and spike–wave complexes. Prior to the onset of light-induced seizures, high-voltage spikes, at the same frequency as the stimulus, appear in all leads of the epileptic EEG. For a short time after a convulsion the EEG of epileptic chickens remains flattened, suggesting decreased electrical activity similar to the postictal depression seen in the EEG of human epileptics.
TL;DR: The "obstruction effect" from the "binding effect", both of which operate to reduce the diffusion coefficient of substances in the myoplasm, are separated with the aid of Wang's theory for diffusion in polyelectrolyte solutions.
Abstract: Intrafiber diffusion of 3HOH, dimethyl-3H-sulfoxide (DMSO), D-14C-sorbitol, and 36Cl was measured along the longitudinal axis of the single muscle fiber (Balanus nubilus) that had been placed insid...
TL;DR: The effect of these peptides on ileal muscle was largely mediated by cholinergic mechanisms, however, it could not be ascertained whether the effect resulted solely from release of acetylcholine by nerve endings or from the participation of acetelcholine mainly as a synergist of the peptides' action on smooth muscle fibers.
Abstract: The mode of action of cholecystokinin (CCK), an octapeptide fragment of CCK, caerulein, and pentagastrin on isolated guinea pig ileal muscle was investigated and their relative potencies determined. On a molar basis, octapeptide-CCK and caerulein were about twice as potent as CCK, whereas pentagastrin and Urecholine were respectively 23 and 46 times less potent. Scopolamine (6.84 × 10−4 M) inhibited the response to all four peptides relatively less than the response to Urecholine. Tetrodotoxin (0.1 μg/ml) inhibited the response to all peptides by 91%. It was concluded that the effect of these peptides on ileal muscle was largely mediated by cholinergic mechanisms. It could not be ascertained, however, whether the effect resulted solely from release of acetylcholine by nerve endings or from the participation of acetylcholine mainly as a synergist of the peptides' action on smooth muscle fibers.
TL;DR: Serum titers evaluated by 3-h and 72-h passive cutaneous anaphylactic reactions indicated that reaginic antibodies were primarily involved, although other immunoglobulins may have played a contributory role.
Abstract: Sprague–Dawley female rats were immunized with egg albumin (EA) in aluminum hydroxide gel (AHG) and with or without Bacillus pertussis vaccine (BPV). Fourteen days later, the animals were anestheti...
TL;DR: Cardiovascular responses occurred in response to marihuana in the absence of intoxication, indicating that they were not psychogenically mediated and inhibition of vagal tone may contribute to the tachycardia seen with marihuan.
Abstract: Twenty-eight subjects, matched by sex and Cannabis experience, received by controlled inhalation under single- and double-blind conditions 600 mg marihuana placebo and marihuana. Forearm, venous and arterial pressures, forearm blood flow, and heart rate were recorded while supine. Derived functions such as "dp/dt", regional arterial resistance, and venous compliance were calculated from these variables. (1) Placebo produced no intoxication or consistent physiological responses. (2) Marihuana produced intoxication in all Cannabis-experienced and half the non-experienced subjects. (3) Cardiovascular responses occurred in response to marihuana in the absence of intoxication, indicating that they were not psychogenically mediated. (4) Inhibition of vagal tone may contribute to the tachycardia seen with marihuana. (5) Reflexly mediated sympathetic responses may be muted in the presence of marihuana.
TL;DR: A modification of the microsphere method for the measurement of the cardiac output distribution in small experimental animals is described, and the results obtained by this modified method in rats agree with those based on the injection of microspheres through the left ventricular cannula.
Abstract: A modification of the microsphere method for the measurement of the cardiac output distribution in small experimental animals is described. The method is suitable for use in both anesthetized and unanesthetized animals. Radioactive microspheres are injected into the left ventricle by cardiac puncture through the closed thorax, which eliminates the need for the cannulation of the left ventricle. The results obtained by this modified method in rats agree with those based on the injection of microspheres through the left ventricular cannula. The described method is suitable for the detection of changes in cardiac output distribution as demonstrated by comparing the results in anesthetized and unanesthetized animals. The cardiac output distribution measured by the microsphere method differs significantly from that based on the rubidium method. The main feature is the fact that the rubidium method tends to overestimate the fractional blood flow to organs with two systems of capillary bed.
TL;DR: The olivo–cerebellar projection has been demonstrated by injections of small volumes of tritiated l-leucine in the inferior olive and a strictly contralateral projection to the cerebellar cortex has been found.
Abstract: The olivo–cerebellar projection has been demonstrated by injections of small volumes of tritiated l-leucine in the inferior olive. A strictly contralateral projection to the cerebellar cortex has b...
TL;DR: Results indicate that angiotensin is involved in drinking in response to extracellular dehydration, and that polyethylene glycol or isoproterenol is used as a solvent for this purpose.
Abstract: The effect of the infusion of antiserum to angiotensin II on extracellular thirst was studied in rats. Drinking induced by the administration of polyethylene glycol or isoproterenol was reduced significantly when antiserum was infused. These results indicate that angiotensin is involved in drinking in response to extracellular dehydration.