A study of the pharmacology of the alimentary tract of the domestic fowl

IN VIVO STUDY OF THE UPPER ALIMENTARY TRACT OF THE FOWL 1. Vagal stimulation produoed contractions of the pre-orop oesophagus, crop and stomaohs (proventrlculus and gizzard) and a fall in arterial blood pressure. Stimulation of the descending oesophageal nerve produced contractions of the pre-orop oesophagus and crop but had no effect on the stomachs or blood pressure. 2. The residual response of the orop to high cervioal vagal stimulation after cutting the recurrent nerve was very small, suggesting that the reourrent nerve supplied the main efferent vagal fibres to the crop. The response of the blood pressure to high cervical vagal stimulation was not affected by cutting the reourrent branch of the vagus and stimulation of the cut reourrent nerve had no effect on the blood pressure, suggesting an absence of cardiac vagal fibres in the recurrent nerve. 3. The effects of stimulation of the vagus or descending oesophageal nerve were potentiated by physostigmine and abolished by hyoscine, suggesting that these nerves are cholinergic; but hexamethonium did not abolish responses to nerve stimulation. 4. In decerebrate chiokens not anaesthetized with pentobarbitone, Intravenous hyosoine abolished the contractions of the oesophagus to vagal or descending oesophageal nerve stimulationTHE CHICKEN ISOLATED OESOPHAGUS 1. Contractions of the ohicken isolated oesophagus produced by stimulation of the vagus and desoending oesophageal nerves were potentiated by physostigmine and abolished by hyoscine (1 to 100 pg/ml) if the duration of stimulation was less than 5 sec, but prolonged stimulation produced contractions not antagonized by hyoscine. The contractions were not abolished by hexaoethonium or tuboourarine even when the nerves were stimulated for less than 5 sec. 2. The oontraotions to nerve stimulation were abolished by oooaine and nerve section, showing that the plain musole was not stimulated directly. Bretylium, mepyramine and methysergide did not antagonize the contraction to nerve stimulation, however, suggesting a lack of involvement of noradrenaline, histamine and 5-hydroxytryptamine, respectively, in the transmission of Impulses producing the byoscine-resistant response. 3. Hyosoine-resistant contractions of the oesophagus to nerve stimulation were obtained from thin external muscle preparations, and previous intravenous injection of hyoscine into ohioks did not prevent subsequently isolated oesophageal preparations from contracting to nerve stimulation, nor did exposure to hyaluronidase modify the effect of hyoscine on the contractions to nerve stimulation, suggesting that resistance to complete block by hyoscine is probably not due to an inability of the drug to diffuse into the preparations. 4. Prolonged nerve stimulation of an isolated oesophagus preparation did not produce a contraction of a preparation of isolated guinea-pig ileum or post-orop chick oesophagus suspended in the same organ hath. 5. It seems possible that small amounts of a slow contracting substanoe were released from the stimulated nerves together with acetylcholine, although suoh a substanoe could not be pharmacologically detected in the bathing solution.SELECTION OF DRUGS FOR BLOCKING ADRENERGIC NEURONES AND A- AND B-RECEPTORS 1. Stimulation of the Remak nerve produced a contraction of the rectum but when the tone of the preparation was raised with acetyl-p-methylcholine, nerve stimulation produeed a transient oontraotion followed by a relaxation. Pharmacological characterisation of the relaxing fibres of the Remak nerve necessitated an in vitro evaluation of drugs which block adrenergic neurones and a- and {3-reoeptora. 2. Propranolol was 26 times as potent as MJ-1999 in blocking the hypogastric nerve of the guinea-pig, but it was 550 times as potent in antagonising the action of isoprenaline on the j3-reoeptors of the chick rectum, showing that propranolol was the drug which was most likely to block (3-reoeptors without producing a nerve block. Moreover, propranolol (0.05 pg/ml) did not antagonize contractions of the chlck rectum to acetylcholine or histamine whereas MJ-1999, at a concentration which was equipotent with propranolol (0.05 i^g/nil) in blocking isoprenaline, antagonized both agonists. Thus propranolol (0.05 jig/ml) was selected for experiments with the ohiok Remak nerve-reotum preparation. 3. Tolazoline, but not phentolamine, potentiated contractions of the guinea-pig vas deferens to hypogastric nerve stimulation, making it an unsuitable drug for antagonizing the action of a neurotransmitter at a-receptors. Furthermore, tolazoline (10 pg/ml) antagonized histamine acting on the chick rectum, whereas phentolamine (0,1 ng/ml), which was equipotent with tolazoline on the rat seminal vesicle, did not. Phentolamine (0,1 pg/ml) was therefore seleoted for blocking the a-receptors of the chick rectum, 4. Bretylium (10 pg/ml) blocked contractions of the guinea-pig vas deferens to hypogastric nerve stimulation, but it did not antagonize contractions of the guinea-pig oesophagus to vagal stimulation or contractions of the ohick rectum to acetylcholine or histamine. Thus bretylium (10 pg/ml) produced a specific block of adrenergic neurones and was used for this purpose in experiments with the ohick isolated Remak nerve-rectum preparation.THE CHICK ISOLATED REMAK NERVE-RECTUM PREPARATION 1. Contractions of the rectum to Remak nerve stimulation resisted complete block by hyosoine as did the contractions of the chick isolated oesophagus to vagal and descending oesophageal nerve stimulation, but the rectal contractions, unlike the oesophageal contractions, were usually abolished by hexamethonium and tubocurarine. 2, Phenylephrine, which typioally stimulates a-reoeptors, produced relaxations of the rectum which were greatly inhibited by propranolol but not phentolamine. A small residual relaxation to phenylephrine persisted in the presence of propranolol, and this was abolished by phentolamine. This suggests that nearly all of the sympathomimetic receptors of the chick rectum were stimulated by phenylephrine and blooked by propranolol, although these two drugs do not normally combine with the same reoeptor. 3. Propranolol only antagonized noradrenaline when isoprenaline and phenylephrine were tested on the same preparation. Furthermore, antagonism of the relaxation of the rectum to Reraak nerve stimulation by propranolol was greatest in experiments where isoprenaline and phenylephrine were tested. This suggests that isoprenaline and/or phenylephrine had an influence on the combination of noradrenaline and/or propranolol with the sympathomimetic receptors. 4. Relaxations of the reotum to Remak nerve stimulation were abolished by a combination of propranolol and phentolamine, and were inhibited by bretylium or by pretreatment with reserpine, suggesting the release of a noradrenaline-like substance from sympathetic fibres contributed by the coeliao plexus.Records obtained from the upper alimentary tract were of the circular muscles in vivo but of the longitudinal musoles in vitr