https://www.gastrojournal.org/article/0016-5085(80)90692-7/pdf

Intestinal blood flow.

With the technical advances of the past few decades, there has been increasing emphasis in neurophysiology and neuropharmacology on studies at the cellular and subcellular levels, as illustrated by most of the chapters in the present volume. The magnitudes and sequences of the electrical signs associated with neuronal activity could be defined accurately only after the development of reliable single unit and intracellular recording techniques. At the same time, the electron microscope has yielded knowledge of the morphological details of nervous tissue well beyond its known physiological correlates. However, the chemistry of the structures and specific reactions involved in nervous function can for the most part be described only at the tissue or relatively gross cellular level, and the cytological details as to where the various reactions occur are largely conjectural.

Cytological Distributions and Physiological Functions of Cholinesterases

1 The presynaptic alpha-adrenoceptors located on the terminals of the cholinergic nerves of the guineapig myenteric plexus have been characterized according to their sensitivities to alpha-adrenoceptor agonists and antagonists.2 Electrical stimulation of the cholinergic nerves supplying the longitudinal muscle of the guinea-pig ileum caused a twitch response. Clonidine caused a concentration-dependent inhibition of the twitch response; the maximum inhibition obtained was 80 to 95% of the twitch response. Oxymetazoline and xylazine were qualitatively similar to clonidine but were about 5 times less potent. Phenylephrine and methoxamine also inhibited the twitch response but were at least 10,000 times less potent than clonidine.3 The twitch-inhibitory effects of clonidine, oxymetazoline and xylazine, but not those of phenylephrine or methoxamine, were reversed by piperoxan (0.3 to 1.0 mug/ml).4 Lysergic acid diethylamide (LSD) inhibited the twitch response, but also increased the basal tone of the ileum. Mepyramine prevented the increase in tone but did not affect the inhibitory action of LSD. Piperoxan or phentolamine only partially antagonized the inhibitory effect of LSD.5 Phentolamine, yohimbine, piperoxan and tolazoline were potent, competitive antagonists of the inhibitory effect of clonidine with pA(2) values of 8.51, 7.78, 7.64 and 6.57 respectively.6 Thymoxamine was a weak antagonist of clonidine; it also antagonized the twitch-inhibitory effect of morphine. Thus, its effect against clonidine is probably not mediated specifically at presynaptic alpha-adrenoceptors.7 Labetalol, itself, depressed the twitch response but did not antagonize the inhibitory effect of clonidine on the residual twitch.8 The results demonstrate that the presynaptic alpha-adrenoceptors in the guinea-pig ileum are of the same type as those located presynaptically in sympathetically innervated tissues. They are alpha(2)-adrenoceptors and are different from those located postsynaptically.

PHARMACOLOGICAL CHARACTERIZATION OF THE PRESYNAPTIC α‐ADRENOCEPTORS REGULATING CHOLINERGIC ACTIVITY IN THE GUINEA‐PIG ILEUM

Pharmacological characterisation of the presynaptic α-adrenoceptor in the rat vas deferens

Muscarinic receptor differentiation

The contractions of the isolated guinea-pig vas deferens in response to stimulation of the sympathetic hypogastric nerve were potentiated by low concentrations and inhibited by high concentrations of the antiadrenaline agents tolazoline, yohimbine, ergotamine, phenoxybenzamine and piperoxan. Eserine potentiated the contractions of the vas deferens produced by hypogastric nerve stimulation. The cholinesterase activity of an extract of vas deferens was decreased by the antiadrenaline agents. The potentiation of responses to sympathetic stimulation by antiadrenaline drugs, which also possess anticholinesterase activity, can be explained on the basis of a cholinergic sympathetic mechanism.

/pdf/the-anticholinesterase-activity-of-some-antiadrenaline-3er81qmsku.pdf

The anticholinesterase activity of some antiadrenaline agents.

It has been shown by others that hemicholinium (α,α'-dimethylethanolamino-4,4'-biacetophenone) inhibits the synthesis of acetylcholine, an effect which is reversed by choline. Hemicholinium produces a failure of response to nerve stimulation in the following sympathetically innervated preparations: guinea-pig isolated vas deferens, rabbit isolated uterus, rabbit isolated colon, perfused rabbit ear, cat isolated atria and the piloerector muscles in the cat's tail. The blocking action of hemicholinium on the responses to postganglionic sympathetic stimulation resembles its blocking action against cholinergic nerve stimulation observed on rabbit isolated atria with vagus nerves, rabbit isolated vagina with pelvic nerves, and guinea-pig isolated diaphragm with phrenic nerve. The failure of transmission produced by hemicholinium in sympathetic nerves and in cholinergic nerves can be reversed by choline. It is suggested that if there were a cholinergic junction at sympathetic nerve endings the mechanism of the blocking action of hemicholinium at these endings could be explained by inhibition of acetylcholine synthesis.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1960.tb00287.x

Transmission failure in sympathetic nerves produced by hemicholinium.

A – Cardiovascular Effects of Choline Esters

A buffer for spectrophotometric enzyme studies.

WHEN a drug is given by intravenous infusion it is not possible to define its lethal dose if it is detoxified rapidly, because the apparent lethal dose will depend on the rate of administration of the drug. This difficulty has been emphasized by Beccari1, who pointed out that in the case of drugs which are rapidly eliminated it is better to define a ‘lethal rate’ of infusion rather than a lethal dose. The problem of deciding at which rate of infusion to determine the lethal dose has always been apparent in the study of cardiac glycosides, and has been accentuated by the earlier need for biological assay of these drugs. The relationship between rate of infusion and lethal dose of cardiac glycosides and aglycones is complex, depending both on the individual drugs and the species used for the determination of toxicity. In the British Pharmacopœia (1958) and the U.S. Pharmacopœia (thirteenth revision) this problem is defined by laying down maximum and minimum times during which each determination of lethal dose must be made. From Table 1 it can be seen that the apparent lethal dose of digoxigenin determined in the guinea pig depends on the time taken to produce death. At the lower rates of infusion in which the time to produce death is prolonged, the apparent lethal dose has the highest values.

M. J. Rand

Papers

The anticholinesterase activity of some antiadrenaline agents.

Transmission failure in sympathetic nerves produced by hemicholinium.

A – Cardiovascular Effects of Choline Esters

A buffer for spectrophotometric enzyme studies.

Effect of the rate of elimination of digoxigenin in the guinea pig on the determination of its lethal dose.