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Physiology and pathophysiology of the lower esophageal sphincter.

The physiologic factors controlling lower esophageal sphincter (LES) function are interrelated in a complex fashion and include the autonomic nerve supply, gastrointestinal hormones, and specific characteristics of the circular smooth muscle at the esophagogastric junction. It might be expected that a defect in any of these three controlling mechanisms would result in a clinically recognizable symptom complex. Abnormalities with either high or low LES pressure have been shown to relate to these specific aspects. Studies of the effects of various foods and other agents which decrease or increase LES pressure are of therapeutic interest in relating to patients with reflux symptoms. Decreases in LES pressure occurring after fat ingestion may explain a mechanism for many cases of fatty food intolerance. Pressure decreases after chocolate ingestion, after smoking, and after alcohol all have strong therapeutic implications in patients with chronic heartburn. Gastric alkalinization will increase pressure for up to one hour in patients with basal sphincter hypotension and reflux symptoms. Recent studies with drugs that work through the cholinergic mechanism have important therapeutic considerations. Anticholinergic agents produce definite decreases in LES pressure and are to provided in treatment of patients with reflux symptoms. On the other hand cholinergic drugs such as bethanechol have been shown to increase LES pressure in normal subjects and in patients with chronic sphincter incompetence. Recently, a double-blind therapeutic trial with bethanechol in patients with chronic heartburn has indicated that this drug, when given on regular basis, is an effective adjunct to therapy in these patients.

Anemia, Pernicious↗

Pharmacological and ionic characterizations of the muscarinic receptors modulating [3H]acetylcholine release from rat cortical synaptosomes.

The muscarinic receptors that modulate acetylcholine release from rat cortical synaptosomes were characterized with respect to sensitivity to drugs that act selectively at M1 or M2 receptor subtypes, as well as to changes in ionic strength and membrane potential. The modulatory receptors appear to be of the M2 type, since they are activated by carbachol, acetylcholine, methacholine, oxotremorine, and bethanechol, but not by pilocarpine, and are blocked by atropine, scopolamine, and gallamine (at high concentrations), but not by pirenzepine or dicyclomine. The ED50S for carbachol, acetylcholine, and oxotremorine are less than 10 microM, suggesting that the high affinity state of the receptor is functional. High ionic strength induced by raising the NaCl concentration has no effect on agonist (oxotremorine) potency, but increases the efficacy of this compound, which disagrees with receptor-binding studies. On the other hand, depolarization with either KCl or with veratridine (20 microM) reduces agonist potencies by approximately an order of magnitude, suggesting a potential mechanism for receptor regulation.

Acetylcholine↗

Ethnopharmacology, phytochemistry and pharmacology: a successful combination in the study of Croton cajucara.

Phytochemical and pharmacological studies of Croton cajucara were oriented by traditional medicine. The stem bark of the mature plant is a rich source of clerodane-type diterpenes: trans-dehydrocrotonin (DCTN), trans-crotonin (CTN), cis-cajucarin B, cajucarin A, cajucarinolide and two novel clerodanes, trans-cajucarin B and sacacarin. In young (18-month-old) plants, the triterpene acetyl aleuritolic acid (AAA) was the major stem bark component and in these the diterpene DCTN was not present. The highest concentration of DCTN (1.4% of dry bark) was detected in 4-6 year-old plants, while 3-year-old plants contained only 0.26% of this diterpene. Three steroids (beta-sitosterol, stigmasterol and sitosterol-3-O-beta-glucoside), two flavonoids (kaempferol 3,4', 7-trimethyl ether and 3,7-dimethyl ether) and one diterpene (cajucarinolide) were isolated from the leaves of this Croton. The main pharmacological activity was correlated with DCTN. This clerodane produced anti-inflammatory and antinociceptive effects and a significant hypoglycemia in alloxan-induced diabetic rats. The compound also reduced the index of gastric lesions induced by restraint-in-cold. Dose-related DCTN and CTN inhibited in vivo the basal acid secretion in pylorus-ligature rats and oxyntic glands isolated from rabbit gastric mucosa, DCTN, CTN or AAA decreased in vitro uptake basal acid secretion induced by histamine and measured with the 14C-aminopyrine uptake method. Uniquely DCTN inhibited 14C-AP uptake induced by bethanechol. The terpenoids, DCTN and AAA, and the chloroform extract of 6-month-old plants reduced gastrointestinal transit in mice. The effects of DCTN and CTN on the survival of mice bearing Sarcoma 180 and Ehrlich carcinoma ascitic tumors, on the proliferation of cultured cells and TNFalpha were determined. DCTN was also evaluated for a possible antioestrogenic activity using the immature rat as a model system for bioassay of oestrogen and for an anti-implantation effect in regularly cycling rats. The biological experiments, using the plant extracts and the terpenoids DCTN, CTN and AAA, are herein discussed.

Animals↗

YF476 is a new potent and selective gastrin/cholecystokinin-B receptor antagonist in vitro and in vivo.

BACKGROUND: We newly synthesized YF476 ((R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2'-pyridyl)-1H-1, 4benzodiazepin-3-yl]-3-(3-methylamino-phenyl)urea) as a gastrin/cholecystokinin-B (CCK-B) receptor antagonist. We investigated the pharmacological profile of YF476 in vitro and in vivo. METHODS: We examined the binding properties of YF476 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, and the effect of YF476 on secretagogue-induced gastric acid secretion in rats and Heidenhain pouch dogs. RESULTS: YF476 replaced the specific binding of [125I]CCK-8 to the rat brain, cloned canine and cloned human gastrin/CCK-B receptors, with Ki values of 0.068, 0.62 and 0.19 nM, respectively. The affinity of YF476 for rat brain gastrin/CCK-B receptor was 4100-fold higher than that for rat pancreatic CCK-A receptor. In anaesthetized rats, intravenous YF476 inhibited pentagastrin-induced acid secretion with an ED50 value of 0.0086 micromol/kg, but did not affect histamine- and bethanechol-induced acid secretion at a dose of 10 micromol/kg. In Heidenhain pouch dogs, intravenous and oral YF476 inhibited pentagastrin-stimulated gastric acid secretion in a dose-dependent manner with ED50 values of 0.018 and 0.020 micromol/kg, respectively, but did not affect histamine-induced acid secretion. CONCLUSION: These results suggest that YF476 is an extremely potent and highly selective gastrin/CCK-B receptor antagonist, and that the gastrin/CCK-B receptor is not involved in histamine- or bethanechol-induced gastric acid secretion in dogs or rats.

3T3 Cells↗

Physiological effects of macrocycle 1 on the rabbit corpus cavernosum.

When the penis is in the flaccid state, the corpus cavernosum smooth muscle is under adrenergic control in order to maintain the sinusoids in a contracted condition (primarily via alpha-adrenergic stimulation). Penile erection is mediated by relaxation of corporal smooth muscle through a variety of direct and indirect mechanisms. Pharmacological agents that either inhibit alpha-adrenergic transmission or facilitate corporal smooth muscle relaxation will be beneficial for penile erection. Preliminary studies on macrocycle 1, a novel bioactive agent, demonstrated that this compound inhibits receptor-stimulated contraction without significantly altering field-stimulated contraction. The current study was designed to determine the physiological effects of macrocycle 1 on the response of the rabbit corpus cavernosum to various forms of stimulation. Sexually mature male New Zealand White rabbits were used in this study. The corpus cavernosum was dissected sharply from the removed penis and two longitudinal strips were prepared for isometric tension studies. Each strip was prestimulated with 200 mumol/l phenylephrine to produce a maximal contraction. The influences of macrocycle 1 (15.6, 62.5, 250, 1,000 mumol/l) on both the contractile response to phenylephrine and the relaxant effects of field stimulation, carbachol, ATP and nitroprusside were determined. The results demonstrated that although basal tension was not altered, the contractile response to phenylephrine was decreased by 5, 18, 47 and 57%, respectively, by the different concentrations of macrocycle 1. The degree of relaxation induced by field stimulation of various frequencies was significantly enhanced by macrocycle 1 in a concentration-dependent manner. Similarly, the degrees of relaxation induced by bethanechol, ATP and nitroprusside were all significantly enhanced in a concentration-dependent manner. The conclusion from this study is that macrocycle 1 significantly inhibits phenylephrine-stimulated contraction and significantly enhances field-stimulated and pharmacologically induced relaxation. Although the mechanisms of action are not clear, its physiological effects on the rabbit corpus cavernosum implicate a potential for the treatment of erectile dysfunction.

Adenosine Triphosphate↗

Mediation of food protein-induced jejunal smooth muscle contraction in sensitized rats.

Alterations in myoelectric and motor activity are important features of food protein-induced intestinal anaphylaxis. To determine the mediator(s) involved, rats were sensitized by injection of egg albumin (10 micrograms ip), and controls were sham sensitized with saline. Fourteen days later the contractility of longitudinally oriented jejunal segments (mucosa intact) was examined in standard tissue baths in response to antigen (Ag) or other agents. Although control and sensitized tissues similarly contracted to stretch, bethanechol, histamine, or 5-hydroxytryptamine (5-HT), Ag contracted only sensitized segments. Contractile response 1) was specific to the sensitizing Ag, as bovine serum albumin did not induce contraction, and 2) could be passively transferred with serum containing specific IgE antibody. Mast cell degranulation after Ag challenge was suggested by a significant loss of granulated mast cells in sensitized compared with control rats challenged with Ag. Concanavalin A, which degranulates mucosal and connective tissue-type mast cells, and compound 48/80, which degranulates only connective tissue-type mast cells, produced a contractile response. Ag-induced contraction was significantly inhibited by the mucosal and connective tissue-type mast cell stabilizer doxantrazole (P less than 0.001) and the connective tissue mast cell stabilizer disodium cromoglycate (P less than 0.05). Diphenhydramine and cimetidine together blocked histamine-induced contraction but failed to affect Ag-induced contraction in sensitized tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

gamma-butyrolactone enhances the activity of GABA in the gastric acid secretion of anesthetized rats.

Influences of gamma-butyrolactone (GBL) on GABA agonists-induced gastric acid secretion were studied in anesthetized rats. GBL potentiated the effect of GABA and GABA agonists on gastric acid secretion, and gamma-hydroxybutyric acid, a metabolite of GBL, tended to enhance the effect of GABA. However, GBL did not influence 2-deoxy-D-glucose- or bethanechol-stimulated acid secretion. A benzodiazepine, diazepam, also increased the secretagogue action of baclofen. A GABA antagonist, bicuculline, but not picrotoxin, inhibited the acid secretion stimulated by the combination of GBL and GABA or muscimol. Aminooxyacetic acid, an inhibitor of GABA transaminase, potentiated the effect of GABA. Dopamine receptor agonists and antagonist did not modify the effect of GABA. Neither GABA mimetic action of GBL nor its influences on the dopaminergic system are involved in the effect of the compound on gastric acid secretion. Although the possibility that GBL inhibits GABA degradation is not excluded, the compound appears to increase the sensitivity of GABA receptor to GABA mimetics in the gastric acid secretion.

4-Butyrolactone↗

Pharmacology of mifentidine, a novel H2-receptor antagonist.

N1-[(4-Imidazolyl)-phenyl]-N2-isopropylformamidine (mifentidine, DA 4577 is a potent and selective H2 antagonist, representative of a new class of compounds, the imidazolylphenyl-formamidines, characterized by a semi-rigid structural conformation. Mifentidine appeared to be a specific and competitive antagonist of several histamine-mediated responses. Thus, in isolated guinea pig atria and ventricles it antagonized histamine chronotropic and dimaprit inotropic effects in a competitive manner providing affinity estimates (pA2) of 7.66 and 7.74, respectively. Mifentidine exerted potent antisecretory effects in: the isolated mouse stomach where it antagonized the acid promoting activity of histamine (EC50 3.28 mumol/l) but not that of bethanechol or db-cAMP (adenosine 3',5'-monophosphate); the lumen perfused stomach of the anaesthetized rat, inhibiting histamine (ED50 0.1 mumol/kg i.v.) and pentagastrin (ED50 0.2 mumol/kg i.v.) stimulated secretion; the pylorus ligated rat (ED50 1.35 mumol/kg i.v.); the gastric fistula dog, reducing the secretagogue effect of pentagastrin (ED50 96 nmol/kg i.v.); the conscious dog equipped with the Heidenhain pouch, where it was effective both following intravenous (ED50 119.7 nmol/kg) and oral administration (ED50 323.8 nmol/kg) in antagonizing histamine action. Mifentidine antisecretory effect, examined in the dog, appeared to last for a significantly longer time than that of ranitidine. Mifentidine was free of cardiovascular effects (on aortic blood pressure and heart rate) when administered repeatedly to the conscious dog at doses far above those needed to suppress acid secretion.

Animals↗

In vitro effects of the long-acting somatostatin analogue SMS 201-995 on electrolyte transport by the rabbit ileum.

We have investigated the in vitro properties of SMS 201-995, a long-acting somatostatin analogue, on electrolyte transport in rabbit ileum. Similar to native somatostatin, serosal addition of this compound inhibits electrogenic anion secretion and stimulates neutral sodium and chloride absorption. Both compounds have similar maximal effects on ion transport; however, the ED50 of SMS 201-995 (2.4 X 10(-10) M) was 60 times less than that for somatostatin. In addition, unlike somatostatin, no inherent tachyphylaxis was observed in response to SMS 201-995. The antisecretory profile of SMS 201-995 was also compared with that of epinephrine. Unlike treatment with epinephrine, pretreatment of tissues with SMS 201-995 did not directly inhibit electrogenic anion secretion stimulated by vasoactive intestinal polypeptide, calcium ionophore A23187, and bethanechol. In contrast, this agent blocked vasoactive intestinal polypeptide and bethanechol inhibition of net sodium absorption. We conclude that SMS 201-995 has several unique in vitro properties that may explain its greater biologic activity compared with that of somatostatin. Its effects on secretagogue-stimulated electrogenic anion secretion and electroneutral NaCl absorption appear to differ.

Absorption↗

Novel acetylcholinesterase inhibitor as increasing agent on rhythmic bladder contractions: SAR of 8-{3-[1-(3-fluorobenzyl)piperidin-4-yl]propanoyl}-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one (TAK-802) and related compounds.

As part of an on-going investigation to develop an increasing agent on rhythmic bladder contractions, 1-aryl-3-(1-benzylpiperidin-4-yl)propanones were synthesized and examined as noncarbamate acetylcholinesterase (AChE) inhibitors. Among compounds with various aryl groups, 1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one derivative 9c was found to possess a potent AChE inhibition activity with an IC(50) value of 1.3nM. The compound 9c increased rhythmic bladder contractions in Guinea pigs and rats without affecting the basal intravesical pressure, which suggests that 9c may be useful for the treatment of voiding dysfunction caused by detrusor underactivity.

Acetylcholinesterase↗

Intermittent catheterization and bladder rehabilitation in spinal cord injury patients.

A review was made of 111 spinal cord injury patients who underwent bladder rehabilitation. The essential mode of treatment was intermittent catheterization. About 91 per cent of the patients were free of the catheter after 3 to 168 days of intermittent catheterization. Acute patients given an initial dosage of 30 to 40 mg. bethanechol chloride 3 times daily for 2 to 3 weeks recovered reflex activity in almost half the period (average of 32 days compared to 79 days). Modified sphincterotomy at the bladder neck was performed in 10 patients. This procedure improved the results to 98 per cent catheter-free reflex bladder status in the group of patients.

Follow-Up Studies↗

Influence of various factors and drugs on cysteamine-induced duodenal ulcers in the rat.

The cysteamine-induced duodenal ulcer reported by Selye et al. was investigated and the optimum conditions for the production of ulcers in rats were established. A single subcutaneous administration of cysteamine between 200 and 500 mg/kg produced ulceration in a dose-dependent manner in the duodenum within 18 hr. Female and older rats were more susceptible to cysteamine than male and younger ones, respectively. Atropine methylbromide inhibited duodenal ulcers induced by cysteamine dose-dependently and pyloric ligation immediately prior to cysteamine dosing completely inhibited ulceration. Tegragastrin or bethanechol increased the severity of cysteamine-induced ulceration. These data suggest that gastric juice may play an important role in the pathogenesis of cysteamine-induced ulcers. The present study provided an excellent animal model for studying the mechanism of duodenal ulcers and screening of antiulcer agents.

Aging↗

Pharmacological characterization of muscarine receptors of PC12 (rat phaeochromocytoma) cells.

The muscarine receptors of PC12 (rat phaeochromocytoma) cells were studied in functional and binding experiments. The catecholamine stores of PC12 cells were labelled by incubation of the cells with tritiated noradrenaline. Muscarinic agonists elicited concentration-dependent release of tritium which consisted overwhelmingly of unchanged 3H-noradrenaline. The rank order of potency was: oxotremorine greater than acetylcholine greater than muscarine = methacholine greater than carbachol greater than bethanechol. The release evoked by carbachol (0.1 mmol/l) was inhibited with high potency by the M1-selective antagonist telenzepine (pKi = 8.82), with intermediate potency by pirenzepine (pKi = 7.00) and with low potency by the M2-selective antagonist AF-DX 116 (pKi = 5.74). The binding of 3H-N-methylscopolamine to PC12 membranes was inhibited by various non-selective and subtype-selective muscarinic antagonists with the following rank order of potency: telenzepine = atropine greater than 4-DAMP greater than dicyclomine greater than pirenzepine greater than HHSiD much greater than AF-DX 116. A similar rank order was obtained for the inhibition by these compounds of 3H-telenzepine binding to M1-receptors in membranes of the cerebral cortex of the guinea pig. The Hill coefficients for inhibition of 3H-N-methylscopolamine binding (to PC12 membranes) by pirenzepine, telenzepine and AF-DX 116 were below unity. Specific binding of both 3H-telenzepine and 3H-N-methylscopolamine to muscarine receptors of PC12 membranes was saturable and of high affinity; the maximal number of binding sites was higher for 3H-N-methylscopolamine than for 3H-telenzepine (calculated for the active (+)enantiomer). PC12 cells are presumably endowed with more than one subtype of muscarine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗

Interaction between adenosine and allergen or compound 48/80 on lung parenchymal strips from actively sensitized Brown Norway rats.

We have investigated the effect of mast cell activation induced by immunological and non-immunological stimuli on the sensitivity to adenosine of parenchymal strips prepared from lungs removed from Brown Norway (BN) rats actively sensitized to ovalbumin. Strips responded to ovalbumin with a biphasic contractile response. Responses to adenosine were markedly increased 30 min after ovalbumin. The first phase of the response to ovalbumin was abolished by the 5-hydroxytryptamine (5-HT)2 receptor antagonist, methysergide and unaffected by the cysteinyl leukotriene receptor antagonist, iralukast. The second phase was abolished by iralukast and unaffected by methysergide. The response to adenosine was markedly reduced by methysergide but not significantly altered by iralukast. Compound 48/80 (condensation product of N-methyl-p-methoxyphenylethylamine with formaldehyde) induced methysergide-sensitive contractions of the parenchymal strip and potentiated adenosine; the augmented response to adenosine was blocked by methysergide. Thus, activation of mast cells in the lung by either immunological or non-immunological stimuli results in augmentation of the mast cell-mediated contractile response to adenosine.

Adenosine↗

Effect of cholecystokinin-B/gastrin receptor blockade on gastric acid secretion in conscious rats.

Gastrin, histamine and acetylcholine are physiological stimuli of gastric acid secretion. The cholecystokinin-B/gastrin receptor antagonists YM022 and RP73870 were used to study the effect of gastrin receptor blockade on acid secretion. Gastrin, histamine, insulin or bethanechol were administered to conscious gastric fistula rats with or without the concomitant intravenous infusion of YM022 or RP73870. Other rats were subjected to pylorus ligation. YM022 and RP73870 inhibited the gastrin-induced acid secretion in a dose- and time-dependent manner; maximal inhibition was observed at a dose of 0.3 mumol.kg-1.hr-1 for both YM022 and RP73870, the ID50 values being 0.02 mumol.kg-1.hr-1 and 0.05 mumol.kg-1.hr-1 for YM022 and RP7870, respectively. At a dose of 0.3 mumol.kg-1.hr-1 YM022 and RP73870 failed to inhibit basal and histamine-, bethanechol-, and insulin-evoked secretion. They also failed to affect the secretion evoked by infusion of a cocktail of maximally effective doses of gastrin-17, histamine and bethanechol. YM022 and RP73870, finally, were without effect on the acid response to pylorus ligation. We suggest that endogenous gastrin in the conscious rat does not contribute to the basal acid secretion and does not participate in the acid response to histamine or to vagus stimulation.

Animals↗

Domperidone improves myogenically transmitted antroduodenal coordination by blocking dopaminergic receptor sites.

An intact guinea-pig gastroduodenal preparation was used to determine the mechanism by which antroduodenal coordination is inhibited by dopamine and improved by domperidone. Domperidone effectively antagonised the inhibitory effects of dopamine in a competitive way. The lack of interference of alpha 1-, alpha 2-, and beta- adrenergic antagonists on the dopaminergic modulation indicates the presence of specific dopamine receptors in the gut wall. Both tetrodotoxin and atropine, but not hexamethonium, prevented the stimulatory effects of domperidone, indicating that intact (postganglionic?) cholinergic intramural nerves were a prerequisite for detecting these effects. In the presence of tetrodotoxin, bethanechol induced coordinated motor patterns, revealing the myogenic control of antroduodenal coordination. When dopamine was tested on coordinated motor patterns as induced by the combination of bethanechol and tetrodotoxin, it no longer inhibited coordination, suggesting that the dopamine receptor is located on nervous structures. It was concluded that dopamine inhibited, and domperidone effectively improved, myogenically controlled antroduodenal coordination via specific dopamine receptors located on nervous structures in the gut wall of the guinea-pig.

Animals↗

[Cathartic activity of spasmogens in mice, rats and guinea pigs (author's transl)].

To examine the effect of spasmogens on propulsive motility in the intestine, cathartic activity of drugs was investigated. Mice, rats and guinea pigs were individually observed in cages with 20 separate small rooms in which a sheet of filter paper covered the botton of case for observation of feces. The effect was evaluated 1 hr after drug administration. Cathartic activity of spasmogens was the most marked in mice followed by rats, but was rarely observed in guinea pigs. Cholinergic drugs and cholinesterase inhibitors had a cathartic effect in mice and rats, but the activity differed. Drugs such as acetylcholine and physostigmine produced a low cathartic activity even at sublethal and lethal doses. Other drugs as bethanechol, pilocarpine and neostigmine had a dose dependent cathartic effect at doses below lethal ones and were found to be clinically useful for intestinal relaxation after laparotomy. Among autacoids which contract the intestine by direct action on smooth muscles, histamine and bradykinin had no cathartic effect in mice and rats. 5-HT and prostaglandin E2 were dose dependent with a marked cathartic effect in both species. 5-HTP produced the same cathartic activity as that seen with 5-HT in mice, but had no cathartic effect in rats. The cathartic effect of BaCl2 was low, but dose dependent in both species. We recommend this method for the study of the effect of various compounds on the propulsive motility of the intestine.

Amines↗

Molecular pharmacological approach to drug actions on the afferent and efferent fibres of the vagal nerve involved in gastric mucosal protection in rats.

BACKGROUND: Gastric mucosal protection is associated with the actions of anti-ulcer drugs or agents affecting on the afferent and/or efferent nerve fibres of the vagal nerve. AIMS: 1. To identify the dose-response curves of drugs (compounds) on the afferent vanilloid-receptor (capsaicin or resiniferatoxin-sensitive) and on efferent secretion (atropine, pirenzepine, cimetidine, ranitidine, famotidine, omeprazole, esomeprazole) basal gastric acid and stimulated gastric secretion in relation to the chemically-induced gastric mucosal damage in rats; 2. To determine the ED50 (pD2) and pA2 on the calculation of affinity and intrinsic affinity curves for these agonists/antagonists, as an indication of relative potency of effects. MATERIALS AND METHODS: The observations were carried out in rats (30 different models). RESULTS: The ED50 values for affinities of capsaicin, resiniferatoxin were obtained in nmol/kg b.w. range, whereas the values were in the nmol/kg to micromol/kg b.w. ranges for effects on the gastric basal, stimulated (bethanechol, pentagastrin, histamine) gastric secretion, and the gastric mucosal damage-produced by different ulcerogenic agents (ethanol, HCl, aspirin, indomethacin). CONCLUSION: From the observations, that agents acting on vanilloid (capsaicin) receptors were the most potent inhibitors of acid secretion and gastric lesions from necrotizing agents, suggests that the capsaicin sensitive afferent nerves have a primary place in the efferent regulated events leading to initiation of gastric mucosal damage.

Afferent Pathways↗