Localization, properties and subtypes of opioid receptors in canine small intestine.
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Animals↗
Biomedical subjects
H D Allescher
Publications and source records attributed to H D Allescher.
Neural reflex of the canine pylorus to intraduodenal acid infusion.
In 29 chloralose-urethane anesthetized dogs, a manometric assembly was inserted through a gastrostomy to monitor pressure of the pyloric region with a sleeve sensor. Antral and duodenal contractions were monitored with both manometric sideholes and serosal strain gauges. An additional tube channel allowed intraduodenal infusions 1-2 cm aborad from the pylorus. Intraluminal infusion of hydrochloric acid (0.1 N, 0.92 ml/min, for 2 min) reproducibly caused activation of motor activity in the pyloric region and peristaltic duodenal activity. Proximal duodenal activity probably contributed to the total phasic response recorded in the pylorus region. Excitatory responses could also be elicited by infusion of phenyl-biguanide (stimulant of sensory nerve endings), but not by control infusions with diluent (Krebs' buffer or saline). The motor response of the pyloric region to intraduodenal acid was blocked by intraduodenal application of 2% xylocaine. Atropine (30 micrograms/kg i.v. and 100 micrograms i.a.) or hexamethonium (10 mg/kg and 1 mg i.a.) markedly reduced or blocked the acid-induced pyloric motor response of this region but propranolol (1.0 mg/kg i.v. and 100 micrograms i.a.), phentolamine (1.5 mg/kg i.v. and 100 micrograms i.a.), or naloxone (200 micrograms/kg and 20 micrograms i.a.) had no effect. We believe these observations show the existence of a reflex from the duodenum to the pylorus in response to intraluminal stimuli mediated by a chain of cholinergic nerves. In the dog, endogenous opioid peptides do not contribute to the excitatory reflex pathway activated by intraduodenal acid or phenyl-biguanide. As intraluminal acid in the duodenum activates this reflex, it may play a role in the physiologic and pathophysiologic role of gastric emptying in this species.
Anesthesia, Local↗
Papilla of Vater: structure and function.
The papilla of Vater is involved in the regulation of bile flow (inhibition and facilitation) into the duodenum and the prevention of reflux into the bile and pancreatic duct system. These functions are achieved by a special muscular, neural and mucosal structure of the papilla of Vater. The mucosa of the papilla of Vater consists of a complicated system of mucosal folds which can function as an anti-reflux valve or might even participate in the regulation of bile outflow. The smooth muscle of the sphincter of Oddi differs anatomically and embryologically from the surrounding duodenal muscle. It shows spontaneous electrical and mechanical activity acting independently from the duodenum but integrated into the overall function of the gastrointestinal tract by myogenic mechanisms, extrinsic and intrinsic nerves and circulating hormones. A spontaneous myogenic electrical activity propagates distally and leads to distally propagating phasic contractions. With endoscopic manometry in humans these phasic contractions as well as basal tone, bile duct pressure and pancreatic duct pressure can be measured. Changes of the basal tone and the phasic activity will alter the flow resistance thus regulating bile flow and inducing gallbladder filling. The most characteristic feature of the sphincter of Oddi is the inhibitory effect of cholecystokinin, which is a powerful contractor of the gallbladder, on the sphincter of Oddi motor activity. Cholecystokinin released in response to intra-duodenal fat and other nutrients might be the physiological stimulus of the increased bile flow post-prandially. The function of other hormones is still rather speculative and their physiological significance awaits further confirmation.
Ampulla of Vater↗
Morphology of the canine pyloric sphincter in relation to function.
The ultrastructure and immunocytochemistry of the canine distal pyloric muscle loop, the pyloric sphincter, were studied. Cells in this muscle were connected by gap junctions, fewer than in the antrum or corpus. The sphincter had a dense innervation and a sparse population of interstitial cells of Cajal. Most such cells were of the circular muscle type but a few were of the type in the myenteric plexus. Nerves were sometimes associated with interstitial cell profiles, but most nerves were neither close to nor associated with interstitial cells nor close to smooth muscle cells. Nerve profiles were characterized by an unusually high proportion of varicosities with a majority or a high proportion of large granular vesicles. Many of these were shown to contain material immunoreactive for vasoactive intestinal polypeptide (VIP) and some had substance P (SP) immunoreactive material. All were presumed to be peptidergic. VIP was present in a higher concentration in this muscle than in adjacent antral or duodenal circular muscle. Interstitial cells of Cajal made gap junctions to smooth muscle and to one another and might provide myogenic pacemaking activity for this muscle, but there was no evidence of a close or special relationship between nerves with VIP or SP and these cells. The absence of close relationships between nerves and either interstitial cells or smooth muscle cells leaves unanswered questions about the structural basis for previous observations of discrete excitatory responses or pyloric sphincter to single stimuli or nerves up to one per second. In conclusion, the structural observations suggest that this muscle has special neural and myogenic control systems and that interstitial cells may function to control myogenic activity of this muscle but not to mediate neural signals.
Animals↗
Inhibitory function of VIP-PHI and galanin in canine pylorus.
Contractions of canine pylorus and adjacent muscles were recorded with antral and duodenal strain gauges and a Dent sleeve manometric assembly with additional side holes in the pylorus. In vivo, vasoactive intestinal polypeptide (VIP) and peptide histamine isoleucine (PHI) given through the gastroepiploic artery inhibited both spontaneous and acetylcholine-induced pyloric contractions, before and after neural blockade with tetrodotoxin. Galanin inhibited only nerve-stimulated contractions. VIP greater than PHI much greater than galanin inhibited pyloric motor activity initiated by field stimulation of duodenal intramural nerves or intraduodenal infusion of 0.1 N HCl. In vitro, forskolin or field stimulation of nerves inhibited contractions of the pyloric muscle induced by various agonists but VIP-PHI failed to inhibit these contractions on two-thirds of the strips. The in vivo results suggest that VIP (or PHI) may be an inhibitory mediator in the pylorus acting directly on smooth muscle. Galanin may inhibit neural excitatory pathways in the pylorus. However, the structures on which VIP and PHI act in vivo may have become nonfunctional in vitro and other mediators account for the neural inhibition observed in isolated strips.
Acetylcholine↗
Biochemical studies on opioid and alpha 2-adrenergic receptors in canine submucosal neurons.
Biochemical information about receptors for adrenergic and opioid neurotransmission in submucosal plexus (SMP) is unavailable. We have purified a fraction P2 enriched in synaptosomes and neuronal membranes (high [3H]saxitoxin binding and high vasoactive intestinal polypeptide immunoreactivity, low activity of 5'-nucleotidase) from the canine small intestine SMP. The synaptosomal fraction (fraction P2) also contained a high density of opioid diprenorphine binding sites of high affinity. [3H]rauwolscine binding was enriched both in fraction P2 and in a microsomal fraction. Competition experiments using several adrenergic and opioid receptor ligands revealed that opioid receptors were approximately 64% mu-, 24% delta-, and 12% kappa-subtypes and that adrenoceptors on fraction P2 were alpha 2-subtype but that there was a heterogeneous population of alpha 2-adrenoceptors. These studies show that a fraction enriched in synaptosomes and neural membranes from the canine intestine SMP contains opioid as well as alpha 2-adrenoceptors, that all three subtypes of opioid receptors seem to be present with mu-receptors predominant, and that subtypes of alpha 2-adrenoceptors appear to be present.
5'-Nucleotidase↗
Distribution of opioid receptors in canine small intestine: implications for function.
Distribution of the binding sites for [3H]diprenorphine, a non-selective opiate ligand, was studied in membrane fractions from longitudinal muscle/myenteric plexus and circular muscle containing deep muscular plexus. [3H]saxitoxin was used as a marker for neuronal plasma membranes and 5'-nucleotidase as a marker for smooth muscle plasma membranes. Saxitoxin binding correlated strongly with diprenorphine binding, but 5'-nucleotidase correlated poorly with diprenorphine or saxitoxin binding in these fractions. Opiate binding sites in membranes of myenteric and deep muscular plexus were of high affinity (Kd = 0.12 and 0.18 nM, respectively) with maximum binding capacity of 400 and 500 fmol/mg protein, respectively. Competition experiments using subtype-selective opiate ligands indicated that all three subtypes of opiate receptors were present in the same ratio of 40-45% mu-subtypes, 40-45% delta-subtypes, and 10-15% kappa-subtypes on both plexuses. Opiate receptors of canine small intestine, therefore, are located primarily or exclusively on nerves with similar distributions in nerve membranes containing only axonal varicosities (deep muscular plexus) as in those containing neurons, dendrites, and varicosities (myenteric plexus).
Animals↗
Effect of the novel cholecystokinin receptor antagonist CR-1392 on cholecystokinin-induced antroduodenal and pyloric motor activity in vivo.
The effects of i.a. injected cholecystokinin (CCK)-octapeptide on pyloric and antroduodenal motility, measured with strain gauges and combined side hole-sleeve manometry, were investigated in 16 dogs in vivo. CCK-octapeptide (OP) induced strong pyloric contractions when injected into the pylorus (threshold of 2 x 10(-13) mol; ED50, 8 x 10(-13) mol). Similar responses were obtained in the distal antrum (threshold, 6 x 10(-13) mol; ED50, 3 x 10(-12) mol) and the proximal duodenum (threshold, 5 x 10(-13) mol; ED50, 3 x 10(-12) mol). The nonsulfated form of CCK-OP was about 2 to 3 log units less potent in eliciting these excitatory responses in the pylorus (threshold, 9 x 10(-10) mol). Atropine shifted the dose-response curve of CCK-OP in pylorus, duodenum and antrum to the right suggesting a neural action of CCK-OP. However, an excitatory effect of CCK-OP was still present after neural blockade with tetrodotoxin i.a. Therefore, there was probably a muscular as well as a neural site of action of CCK-OP in these tissues. Systemic application of the novel CCK-antagonist CR-1392 in a dose of 1.2 mg/kg i.v. plus 100 micrograms i.a. shifted the dose-response curve of CCK-OP 1 log unit to the right without affecting the dose-response curve to acetylcholine. This dose of CR-1392 did not interfere with the pyloric motor responses to duodenal field stimulation or to intraduodenal acid infusion. These results demonstrate the dual peripheral action on nerve and muscle of CCK-OP in the pylorus in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Modulation of pyloric motor activity via adrenergic receptors.
The influences of adrenergic nerves on pyloric motor function and the locus and types of receptors involved were examined. Using glyoxylic acid fluorescence a dense adrenergic innervation of the inner pyloric muscle ring was demonstrated. Pyloric motor activity was monitored while close i.a. injections of a selective alpha-1 adrenoceptor agonist, phenylephrine, or a selective alpha-2 adrenoceptor agonist, B-HT-920, were given. Neither agonist affected basal pyloric motor activity, but both inhibited pyloric activity when it was stimulated by duodenal field stimulation or by intraduodenal acid infusion. The actions of each of the inhibitory agonists, phenylephrine or B-HT-920, were blocked selectively by prazosin or rauwolscine, respectively. Injection of isoproterenol usually had no effect or excited basal pyloric activity. This excitation could be antagonized selectively by propranolol or by atropine. Injection of isoproterenol after neural blockade by tetrodotoxin inhibited pyloric motor activity. Receptor binding studies carried out with subcellular nerve or muscle enriched membrane fractions of canine pyloric muscle with [3H]prazosin, [3H]rauwolscine and [125I]cyanopindolol revealed a dual location of alpha-1, alpha-2 and beta receptors on both nerve membranes and smooth muscle membranes. These results suggest that adrenergic effects on the pyloric muscle can be exerted by pre- and postsynaptic beta receptors which, respectively, excite by releasing acetylcholine and inhibit by acting on receptors on the pyloric muscle. Also inhibitory alpha-1 and alpha-2 receptors are present on cholinergic nerves. The functions of postsynaptic alpha-1 and alpha-2 adrenoceptor binding sites on smooth muscle are so far unknown.
Animals↗
Effect of naloxone on vagally-induced gastric acid secretion in rats.
Previous studies in man and dogs have demonstrated that endogenous opioids participate in the stimulation of cephalic phase gastric acid secretion during indirect activation of the vagus. Since the effect of naloxone during direct vagal activation is unknown gastric acid secretion was assessed during electrical stimulation of the distal cut ends of both vagal nerves. In overnight fasted anesthetized rats the distal ends of the bisectioned cervical vagi were stimulated with 10V, 5Hz, 5 msec for 15 min. Vagal stimulation elicited an increase of gastric acid secretion by 5.6 mumol/min. Naloxone (1 mumol/kg.h) augmented gastric acid secretion significantly. Since this effect of naloxone was in contrast to previous data possible mechanisms of action of naloxone were examined that might help to explain this apparently inhibitory action of endogenous opioids on vagally-induced gastric acid secretion. The additional infusion of atropine or hexamethonium abolished the stimulatory effect of naloxone on vagally-induced acid secretion completely indicating that the action of naloxone depends on cholinergic background activity. Combined blockade of alpha- and beta-adrenergic receptors with phetolamine and propanolol reduced vagally-induced acid secretion in controls and during naloxone to a similar degree. Both adrenergic blocking agents also reduced the residual acid secretion observed during atropine or atropine + naloxone infusion. Measurements of plasma gastrin levels suggested that the naloxone-induced changes of acid secretion were not due to alterations of gastrin secretion. In summary these data demonstrate that vagally-induced acid secretion in anesthetized rats is largely due to cholinergic mechanisms with a small but separate contribution of adrenergic mechanisms. Endogenous opioids are activated during peripheral vagal stimulation attenuating vagally-induced acid secretion by modulation of cholinergic but not adrenergic mechanisms.
Animals↗
Extrinsic and intrinsic neural control of pyloric sphincter pressure in the dog.
1. In chloralose-urethane-anaesthetized dogs a manometric assembly was inserted via a gastrostomy to monitor pyloric pressure with a sleeve sensor. Antral and duodenal contractions were monitored with both manometric side holes and serosal strain gauges. 2. Subserosal silver wire electrodes were placed in the antrum 5 cm orad and the duodenum 3 cm aborad to the pylorus to facilitate field stimulation of intramural nerves. 3. The pylorus exerted spontaneous tone (10.8 +/- 4.8 mmHg) with phasic contractions occurring at a rate varying from 1-5 min-1 and, at times, with a superimposed higher frequency up to 15 min-1. Atropine (30 micrograms kg-1 I.V. and 10 micrograms I.A.) reduced and tetrodotoxin (50-100 micrograms I.A.) enhanced the phasic activity significantly. 4. Bilateral cervical vagal section had no consistent influence on pyloric motility. 5. Stimulation of the distal ends of the cervical vagal nerves at low frequencies (0.2-0.5 Hz, 1-3 ms, 20 V) induced phasic pyloric contractions, which were abolished by atropine or hexamethonium (10 mg kg-1 I.V. and 1 mg I.A.). Higher frequencies (greater than 0.7 Hz) of stimulation inhibited both phasic and tonic contractions and this inhibition was unaffected by atropine, hexamethonium, phentolamine (1.5 mg kg-1 I.V. and 100 micrograms I.A.) or propranolol (1 mg kg-1 I.V. and 100 micrograms I.A.). All neural responses were blocked by tetrodotoxin (50-100 micrograms I.A.). 6. Duodenal field stimulation (0.2-5 Hz, 0.5 ms, 40 V) induced strong phasic and tonic contractions in the pylorus. This excitation was blocked by atropine, hexamethonium, tetrodotoxin (50-100 micrograms I.A.) or duodenal transection orad to the stimulating electrodes. 7. Antral field stimulation (0.5-1 Hz, 0.5 ms, 40 V) completely abolished phasic activity in the pylorus and reduced tonic activity, regardless of whether the contractile activity was spontaneous or induced by neural stimulation. This inhibitory action was unaffected by atropine, hexamethonium or propranolol but was blocked by tetrodotoxin and antral transection aborad to the stimulating electrodes. Phentolamine attenuated the inhibitory effect of antral field stimulation on pyloric motility. 8. It is concluded that the distal canine pylorus exhibits myogenic tone and phasic activity which is modulated by extrinsic and intrinsic nerve pathways. Vagal nerves contain fibres, activated by different stimulus parameters which can either excite or inhibit pyloric activity. Activation of antral nerves inhibits pyloric activity, with both non-adrenergic, non-cholinergic and phentolamine-sensitive pathways contributing to this inhibitory response.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Inhibitory opioid receptors in canine pylorus.
In 18 anesthetized dogs, antroduodenal and pyloric motility was monitored in vivo by a sleeve and perfused side-hole manometric assembly and by antral and duodenal serosal strain gauges. Close intra-arterial injection to the pylorus of dynorphin-(1-13) (Dyn) for kappa-receptors, [D-Pen2,5]enkephalin (DPen2,5-Enk) for delta-receptors, and [N-Me-Phe3-D-Pro4]morphiceptin (PL017) and [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO) for mu-receptors showed no excitatory effect in the pylorus. When pyloric motor activity was increased by duodenal field stimulation 3-5 cm aboaad from the pylorus, Dyn greater than DPen2,5-Enk greater than DAGO produced a dose-dependent inhibition of the pyloric motor activity. Naloxone (200 micrograms/kg iv and 20 micrograms ia) had no effect on the pyloric excitation due to duodenal field stimulation, but it reduced the inhibitory response of intra-arterially injected opioids. In addition, opioid binding ([3H]diprenorphine) in microsomal and mitochondrial fractions from the inner circular muscle ring of the pylorus showed a distribution similar to the neuronal marker [3H]saxitoxin but no correlation to the plasma membrane marker 5'-nucleotidase. These results suggest the existence of inhibitory opioid receptors (kappa- and delta-receptors) on excitatory neurons in the intestinal neuronal pathway, which activates the canine pylorus.
Animals↗
Characteristics of canine lower esophageal sphincter: a new electrophysiological tool.
The canine lower esophageal sphincter (LES) was evaluated as a model for investigation of the electrophysiology of nonadrenergic noncholinergic neurotransmission. The LES contained a dense collection of gap junctions and a moderate number of nerves located at the periphery of muscle bundles, which are often associated with interstitial cells of Cajal. These cells make gap junctions with one another and with smooth muscle cells. The nerve varicosities contained many large dense cored vesicles. In vitro the LES produced spontaneous active tone and relaxed to field stimulation that was blocked by tetrodotoxin (TTX). Increase of stimulus duration or frequency produced a partially TTX-insensitive sphincter relaxation. Basal tone and nerve-mediated relaxation were unaffected by cholinergic, histaminergic, or adrenergic antagonists. Acetylcholine, carbachol, or histamine caused TTX-insensitive contractions mediated by M2- and H1-receptors, respectively. Vasoactive intestinal peptide (10(-6) M) and isoproterenol (10(-6) M) relaxed the LES to the same extent as field stimulation. In the double sucrose gap this tissue regularly produced inhibitory junction potentials when field stimulated. The canine LES has appropriate morphological and pharmacological properties for the electrophysiological study of nonadrenergic noncholinergic neural responses, their mechanisms, and mediators.
Animals↗
[3H]saxitoxin as a marker for canine deep muscular plexus neurons.
The objectives of this study are 1) to examine the potential of [3H]saxitoxin binding as a marker for the neuronal membranes in canine small intestinal muscle membrane preparations, 2) to develop a synaptosomal preparation from deep muscular plexus, and 3) to partially characterize [3H]saxitoxin binding to this fraction. A purified synaptosomal fraction, relatively low in the smooth muscle plasma membrane marker enzyme 5'-nucleotidase but enriched in [3H]saxitoxin binding (2,592 fmol/mg), was obtained on sucrose density gradient. Vasoactive intestinal peptide immunoreactivity was also highest (51.82 pmol/mg protein) in this fraction. The binding was rapid at 20 degrees C with quick and complete dissociation after the addition of excess unlabeled tetrodotoxin (TTX). Scatchard analysis of the saturation binding data revealed a single population of binding sites (Bmax = 5,705 fmol/mg protein). The affinity constants calculated from the kinetic and saturation data were in close agreement (Kd = 0.26 and 0.69 nM, respectively). TTX competed for the binding (Ki = 2.1 nM), whereas veratridine and guanidinium hydrochloride did not. Monovalent and divalent cations had differential effects on the binding.
Animals↗
Effect of somatostatin on skin lesions and concentrations of plasma amino acids in a patient with glucagonoma-syndrome.
A case of glucagonoma syndrome in a 58-year-old male patient who had the typical skin lesions associated with severe hypoaminoacidemia is described. The decrease in amino acids has been proposed to be causally related to the dermatosis. Furthermore, it has been shown previously that somatostatin rapidly improves skin lesions in glucagonoma patients. Therefore, plasma amino acid levels were determined before and during an infusion of somatostatin prior to surgical removal of the tumor in the tail of the pancreas. During somatostatin infusion in combination with total parenteral nutrition, 10 out of 22 amino acids were in the normal range. Thus it seems unlikely that normalization of amino acid levels is responsible for the rapid improvement in skin lesions in glucagonoma patients. On the other hand it cannot be excluded that partial normalization of amino acids contributed to the observed healing process. Nevertheless, somatostatin administered prior to surgery is a useful therapeutic regimen in these patients.
Adenoma, Islet Cell↗
Local actions of trimebutine maleate in canine small intestine.
A study of the local actions of trimebutine (TMB) maleate and its N-diesmethyl metabolite (TMB-M) was carried out in the gastrointestinal tract of anesthetized dogs. In the unstimulated small intestine, but not in the stomach or colon, i.a. TMB and TMB-M caused activation of circular muscle. Like the activation by i.a. [Met5]-enkephalin, this was antagonized by naloxone. In field-stimulated segments of stomach and small intestine circular muscle, TMB or TMB-M, like dynorphin-1-13 or [Met5]-enkephalin, inhibited the phasic and tonic contractions which were mediated mostly by cholinergic, postganglionic nerves. However, the inhibitory effects of dynorphin-1-13 or [Met5]-enkephalin on small intestine were antagonized by naloxone whereas those of TMB sometimes or those of TMB-M usually were not. TMB or TMB-M did not affect responses to i.a. acetylcholine, but high doses reduced the contractile responses to subsequent field stimulation and excitatory responses to [Met5]-enkephalin. We concluded that the excitatory local actions of TMB or TMB-M on small intestine involved opioid receptors probably of the mu or delta types. Inhibitory local actions on nerve-mediated responses, however, may not have involved opioid receptors. Comparison of these data to results when TMB or TMB-M were given i.v. suggests that these agents also have peripheral actions to affect gastrointestinal motility at sites outside the gastrointestinal tract.
Animals↗
Effect of atrial peptide on gastric acid secretion in rats.
The effect of synthetic rat atriopeptin (AP) II was examined on basal, vagally and carbachol-induced gastric acid secretion in anesthetized rats. AP II infusion, at stepwise increasing doses of 2, 20 and 100 ng/kg/min, had no effect on basal acid secretion. At doses of 2 and 20 ng/kg/min, AP II augmented vagally induced acid secretion significantly. The secretory response to vagal stimulation + AP II 20 ng/kg/min was completely abolished by atropine. In contrast a higher dose of AP II (50 ng/kg/h) reduced vagally induced acid secretion significantly. This dose of AP II also reduced acid secretion during direct cholinergic stimulation by carbachol, while the lower dose of 20 ng/kg/min had no effect on carbachol-induced acid secretion. The present data demonstrate for the first time an effect of atrial peptide on gastric acid secretion. At lower doses AP II augments the vagal influence on parietal cell function perhaps by augmenting vagally induced acetylcholine release. At higher doses AP II exerts an inhibitory effect on parietal cell function during vagally and carbachol-induced acid secretion, suggesting different and as yet unknown mechanisms of action. These results raise the possibility that the heart can exert a hormonally mediated influence on the regulation of gastric acid secretion.
Animals↗
Ultrastructural localization of VIP-immunoreactivity in canine distal oesophagus.
The localization of vasoactive intestinal polypeptide (VIP) immunoreactivity in canine distal oesophagus was studied using different fixation and embedding procedures and labelling with protein A-gold. The retention of immunoreactivity and the preservation of ultrastructure was best after fixation with a mixture of 0.1% glutaraldehyde and 4% paraformaldehyde, and embedding in 'LR White' resin using the 'cold-cured' method. VIP immunoreactivity was localized exclusively over large granular vesicles in the myenteric plexus and in nerves of the circular muscle. Most varicose profiles in circular muscle were labelled, but some large granular vesicles in the same profiles which contained labelled vesicles as well as some varicose profiles with large granular vesicles were unlabelled. From these data it was uncertain whether unlabelled large granular vesicles contained VIP or other neuropeptides. A striking finding was the dense and close innervation of the interstitial cells of Cajal with nerve containing VIP-labelled large granular vesicles. This finding is consistent with earlier suggestions that VIP-immunoreactive nerves may innervate these cells which are in gap junction contact with smooth muscle and that this arrangement may be involved in the transmission of non-adrenergic, non-cholinergic nerve activity in distal oesophagus.
Animals↗