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PubMed1992

Pituitary adenylate cyclase activating polypeptide-27 (PACAP-27) inhibits pentagastrin-stimulated gastric acid secretion in conscious rats.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel neuropeptide and has two amidated forms, PACAP-27 and PACAP-38. Its chemical structure is similar to that of vasoactive intestinal peptide (VIP). In our previous studies, we found that PACAP has a stimulatory effect on rat exocrine pancreas secretion and an inhibitory effect on rat gastrointestinal motility. These effects of PACAP-27 were greater than those of PACAP-38 and VIP. In the present study, we examined the effect of PACAP-27 on basal and pentagastrin (PG)-stimulated gastric acid secretion in conscious rats and compared its effect with that of VIP. Rats were equipped with a chronic gastric fistula and a permanent IV line and separately housed in metabolic cages. The effects of PACAP-27 and VIP at doses of 1.25, 2.5, 5 and 10 nmol/kg/h on basal and PG (24 micrograms/kg/h)-stimulated gastric acid secretion were tested. Our results showed that: (1) VIP had no significant effect on basal and PG-stimulated gastric acid secretion at the tested doses. (2) PACAP-27 had no effect on basal acid secretion but had a dose-dependent inhibitory effect on PG-stimulated gastric acid secretion. The highest inhibition by PACAP-27, 68.2 + 8.1%, was achieved at 5 nmol/kg/h. We suggest that PACAP may have a regulatory role in gastric acid secretion.

Animals↗

PubMed1994

Galanin-induced relaxation in gastric smooth muscle cells is mediated by cyclic AMP.

Galanin has numerous effects on gastrointestinal motility in different species; however, its cellular basis of action in mediating these effects is unclear. Dispersed gastric smooth muscle cells have been shown to possess high-affinity galanin receptors that increase cAMP and cause relaxation. Recent studies show some smooth muscle relaxants such as VIP cause relaxation by both cAMP-dependent and -independent mechanisms. It is unknown if galanin's cellular basis of relaxation is similar or different from that of VIP. To investigate galanin's relaxant effect and compare it to VIP's effect, dispersed smooth muscle cells from guinea pig stomach were prepared by collagenase digestion. The mean length in resting cells was 110 +/- 2 microns and, with carbachol treatment, contracted to 89 +/- 2 microns. VIP and galanin alone had no effect on cell length, but each caused a dose-dependent inhibition of carbachol-induced contraction and both had an EC50 of 3-7 nM. Galanin (1 microM) and VIP (1 microM) increased cellular cAMP from 118 +/- 10 pmol/10(6) cells in control to 212 +/- 14 and 214 +/- 12 pmol/10(6) cells, respectively. The protein kinase A inhibitor, Rp-cAMPS, at 100 microM, completely inhibited the relaxant effect of an EC50 concentration of galanin (3 nM), but only inhibited that by VIP by 80% (p < 0.05). Adding the nitric oxide inhibitor, L-NNA (NG-nitro-L-arginine), at 100 microM did not alter the length of resting cells or inhibit carbachol-induced contraction. However, L-NNA (100 microM) decreased VIP-induced relaxation by 45%, whereas it had no effect on galanin-induced relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Glycaemic response and hydrogen production to blenderised and polymeric enteral nutrition formulas.

Complete enteral nutrition preparations include blenderised formulas based on natural foods with some fibre content and also low-residue polymeric formulas. This study examines the effect of the different fibre content of two commercial formulas (6.4 g/l and 0.25 g/l) on glycaemic and insulin response and hydrogen production in the colon during constant rate administration in 11 normal subjects. No difference in serum glucose and insulin levels was found. No rise in hydrogen production was detected with either formula suggesting no carbohydrate malabsorption. The quantity or nature of fibre present in blenderised formulas does not modify the pattern of carbohydrate absorption compared to a low-residue polymeric formula. However, this does not preclude other possible physiological effects of fibre content upon gastrointestinal motility and function.

Journal Article↗

PubMed1982

A study of the concentrations of substance P and neurotensin in the gastrointestinal tract of various mammals.

Immunoreactive substance P and neurotensin in extracts of the digestive tract of man, cat, guinea-pig, pig, rabbit, and rat were measured by radioimmunoassay using antisera directed against the C-terminal portions of the two peptides. In all species except the cat, the concentrations of substance P were highest in the small intestine, intermediate in the large intestine and lowest in the stomach and oesophagus: the digestive tract of the cat displayed a rather even distribution of substance P. As observed in the ileum of guinea-pig, rabbit, and rat, the external muscle layer including the myenteric plexus contained 2-5 times higher concentrations of substance P than the whole ileal wall, whereas the substance P concentrations in the mucosa were only about one sixth of those in the whole wall. High performance liquid chromatography of extracts of human, feline and rabbit ileum showed that all the immunoreactive substance P eluted at the positions of substance P and substance P sulfoxide. The distribution of immunoreactive neurotensin along the digestive system of all six species was very similar. The highest concentrations of neurotensin were measured in the distal part of the small intestine, whereas the large intestine, stomach and oesophagus contained only low concentrations of neurotensin relative to the concentrations in the ileum. As examined in the ileum of guinea-pig, rabbit, and rat, the mucosa exhibited 2.5-4 times higher concentrations of neurotensin than the whole ileal wall, while the concentrations of neutrotensin in the external muscle layer including the myenteric plexus were only 4-20% of those in the whole wall. High performance liquid chromatography of the immunoreactive neurotensin extracted from the cat ileum yielded a single peak corresponding to neurotensin while the immunoreactive neurotensin extracted from the ileum of man and rabbit was eluted in two peaks, 55 and 72% of the recovered immunoreactivity, respectively, corresponding to neurotensin. These findings are in line with the proposed roles of substance P in the neural, and neurotensin in the endocrine, control and maintenance of gastrointestinal motility.

Animals↗

PubMed1986

The effects of acute and chronic ingestion of ethanol on the autonomic nervous system.

Evidence is reviewed linking clinical effects of ethanol with actions on the sympathetic and parasympathetic nervous systems. The studies reported include a series of investigations by the authors. Acutely, ethanol causes peripheral vasodilation and may also result in changes in heart rate and blood pressure. Ethanol may contribute to acute problems which may present clinically, including micturition syncope, accidental hypothermia and facial flushing. However, increased sympathetic nervous activity plays a role in causing hypertension and other symptoms during ethanol withdrawal in chronic alcoholics. Some chronic alcoholics may have neuropathy involving sympathetic nerves, and this can result in distal sweating loss and occasionally in orthostatic hypotension. Also, hypothalamic lesions associated with Wernicke's encephalopathy may result in hypothermia. Neuropathy involving parasympathetic nerves in not uncommon in alcoholics with other evidence of nervous system damage, but it is generally asymptomatic. Occasionally, vagal neuropathy may cause disorder of gastrointestinal motility, and neuropathy affecting the sacral innervation may be a factor in alcoholic impotence.

Alcoholic Intoxication↗

PubMed1996

Skeletal, cardiac, and smooth muscle failure in Duchenne muscular dystrophy.

The goals of this study were to describe the clinical course of skeletal, cardiac, and gastrointestinal muscle manifestations and trends in age at diagnosis and survival of Duchenne muscular dystrophy (DMD) patients. A retrospective cohort of 33 male patients with DMD, born between 1953 and 1983 and followed at the Mayo Clinic during their second decade of life, was studied. The mean age at DMD diagnosis was 4.6 years. Skeletal muscle weakness present in all patients at diagnosis progressed to wheelchair dependency in 32 patients (97%) by the age of 13 years (median age 10 years). Cardiac muscle failure developed in 5 patients (15%) (median age 21.5 years). Smooth muscle manifestations related to the digestive and urinary tracts occurred in 7 (21%) and 2 (6%) patients (median age 15 years), respectively. The gastrointestinal dilatations were primary in 2 patients or secondary to surgery or acute respiratory illness in 5 patients. By the end of the study period, 17 deaths had occurred (median age 17 years). Over time, there was a decrease in the time to DMD diagnosis (P = .05) but no significant change in survival (P = .44). Cardiac and smooth muscle manifestations occur late in the course of DMD. Clinical gastrointestinal symptoms related to smooth muscle function most often were secondary to surgery or a respiratory illness. In recent years, the diagnosis of DMD has been made at a younger age, but survival has not changed.

Adolescent↗

PubMed1994

Expanding uses of octreotide.

This chapter reviews the therapeutic use of octreotide in a variety of pancreatic disorders, including acute pancreatitis, in the prevention of postoperative and post-ERCP pancreatitis, in the control of postoperative pancreatic fistulae, and in chronic pancreatitis for the control of pain and of pseudocysts and ascites. The review also discusses the use of octreotide in intestinal disorders of motility, gastrointestinal bleeding, intestinal fistulae and refractory diarrhoea, including the diarrhoeas of AIDS, diabetes, short gut, chemotherapy, ileostomy and gastric surgery. The use of octreotide in neuroendocrine tumours, both for therapy and diagnostic imaging, is reviewed briefly. The paucity of adequately controlled studies in many of these situations is indicated and the potential usefulness of octreotide estimated.

Humans↗

PubMed1991

Influence of prostaglandin E2 infusion on gastrointestinal electrical activity in the conscious piglet.

In 5 conscious piglets with implanted electrodes in the antrum pylori, duodenum, jejunum and ileum, electromyographic activity was recorded daily on a multichannel recorder with a time constant of 0.03 s for intestinal and of 1 s for gastric recordings, and simultaneously integrated at 20 s intervals. PGE2 was infused for 2 h in relatively low doses of 0.1 and 1 microgram/kg/min, to avoid excessive hypersecretion, which would disguise direct effects. Each dose was tested once in each animal with a 1 week interval. Infusion of 0.1 microgram/kg/min revealed no significant changes in antral and small intestinal electrical activity. One microgram/kg/min however induced a strong depression of fast oscillations until the end of the infusion and prolongation of the inhibitory phase in the antrum following a duodenal phase of regular spiking activity. Intestinal segments displayed a prolongation of the quiescent phase and a decrease in the integrated area curve of the phase of irregular spiking activity. Recurrence of the phase of regular spiking activity was unaltered in either segment. These data suggest that the direct effect of PGE2 on gastrointestinal motility in the piglet is a partial inhibition of intestinal contractions.

Analysis of Variance↗

PubMed1996

Pharmacology of serotonin as related to anesthesia.

Serotonin (5-hydroxytryptamine) is an important biogenic amine that fulfills the role of neurotransmitter and neuromodulator. It has been a focus of interest during the last decade. Its diversity of pharmacologic actions is related to a wide variety of receptors and effector mechanisms. Seven serotonin receptor families have been identified thus far. They are genetically different transmembrane proteins composed of several hundred amino acids. The majority of these are G-protein-coupled, except the 5-HT3 receptors, which are directly ligand gated to fast ion channels. Serotonin is widely distributed in the body within the central and peripheral nervous systems, smooth muscles, and platelets, in particular. Consequently, its effects manifest mainly in these organs and influence a wide variety of neural, vascular, smooth muscle, and platelet functions. (Melatonin, a physiologically active metabolite of serotonin, is also instrumental in affecting many neural and hormonal functions.) Several selective agonists and particularly many selective antagonists have been developed for serotonin, which helped the serotonin receptor subtype classification. Some of these drugs are also used therapeutically in the treatment of migraine (eg, sumatriptan, which is a 5-HT1 receptor agonist), vascular disorders (5-HT2 antagonists), and nausea and vomiting (5-HT3 antagonists, eg, dolasetron, granisetron, ondansetron, and tropisetron), and have been investigated in gastrointestinal motility disorders (5-HT4 antagonists) and behavioral psychopathologies (5-HT1 agonists and 5-HT2-4 antagonists). Serotonin reuptake inhibitors are of particular clinical importance in the treatment of psychological illness. Future use of these drugs is also envisioned in the treatment of certain types of pain syndromes. Awareness of the serotonergic drugs and the recognition of possible drug interactions among drugs that influence serotonergic mechanisms in humans are becoming increasingly important in the practice of anesthesiology.

Anesthetics↗

PubMed2003

Which stoma works better for colonic dysmotility in the spinal cord injured patient?

BACKGROUND: The formation of an intestinal stoma is very effective in the treatment of colonic dysmotility associated with spinal cord injury (SCI). Little is known about the difference in the long-term outcome among left-sided colostomies, right-sided colostomies, and ileostomies in this patient population. METHODS: The records of 45 SCI patients with intestinal stomas at our institution were reviewed retrospectively. Operative details and preoperative colonic transit times (CTT) were recorded. Patients who were alive and available were interviewed using a questionnaire designed to assess the quality of life (QOL), health status, and time to bowel care before and after stoma formation. RESULTS: Between 1976 and 2002, 45 patients underwent a total of 48 intestinal stomas. A left-sided colostomy (LC) was formed in 21 patients, right-sided colostomy (RC) in 20, and ileostomy (IL) in 7. Three of the patients in the RC group ultimately underwent total abdominal colectomy and ileostomy. The indications for stoma formation and CTT were different in the three groups. Bloating, constipation, chronic abdominal pain, difficulty evacuation with prolonged CTT was the main indication in 95% of patients in the RC group, 43% of patients in the LC group, and 29% in the IL group. Management of complicated decubitus ulcers, perineal and pelvic wounds was the primary indication in 43% of patients in the LC group, 5% in the RC group, and none in the IL group. Preoperative total and right CTTs were longer in the RC group compared with the LC group: 127.5 versus 83.1 hours (P <0.05) and 53.7 versus 28.5 hours (P <0.05), respectively. Eighty-two percent of patients (37 of 45) were interviewed at a mean follow-up of 5.5 years after stoma formation. Most patients who were interviewed were satisfied with their stoma (RC, 88%; LC, 100%; IL, 83%) and the majority would have preferred to have the stoma earlier (RC, 63%; LC, 77%; and IL, 63%). The QOL index significantly improved in all groups (RC, 49 to 79, P <0.05; LC, 50 to 86, P <0.05; and IL, 60 to 82, P <0.05), as well as the health status index (RC, 58 to 83, P <0.05; LC, 63 to 92, P <0.05; IL, 61 to 88, P <0.05). The average daily time to bowel care was significantly shortened in all groups (RC, 102 to 11 minutes, P <0.05; LC, 123 to 18 minutes, P <0.05; and IL, 73 to 13 minutes, P <0.05.). CONCLUSIONS: Regardless of the type of stoma, most patients had functional improvement postoperatively. Patients who underwent RC had longer CTT and more chronic symptoms related to colonic dysmotility, reflecting the preoperative selection bias. The successful outcome noted in all groups suggests that preoperative symptoms and CTT studies may have been helpful in optimal choice of stoma site selection.

Colonic Diseases, Functional↗

PubMed2005

Female, but not male, serotonin reuptake transporter (5-HTT) knockout mice exhibit bladder instability.

Correlations exist between the incidence of depression, irritable bowel syndrome (IBS) and overactive bladder [Masand, P.S., Kaplan, D.S., Gupta, S., Bhandary, A.N., Nasra, G.S., Kline, M.D., Margo, K.L., 1995. Major depression and irritable bowel syndrome: is there a relationship? J. Clin. Psychiatry 56, 363-367.; Cukier, J.M., Cortina-Borja, M., Brading, A.F., 1997. A case-control study to examine any association between idiopathic detrusor instability and gastrointestinal tract disorder, and between irritable bowel syndrome and urinary tract disorder. Br. J. Urol. 79, 865-878.; Monga, A.K., Marrero, J.M., Stanton, S.L., Lemieux, M.C., Maxwell, J.D., 1997. Is there an irritable bladder in the irritable bowel syndrome? Br. J. Obstet. Gynaecol. 104, 1409-1412.; Zorn, B.H., Montgomery, H., Pieper, K., Gray, M., Steers, W.D., 1999. Urinary incontinence and depression. J. Urol. 162, 82-84.]. Furthermore, alterations in serotonergic neurotransmission may play a common role in the etiology of these disorders. Serotonin reuptake transporter knockout mice (5-HTT(-/-)) display phenotypes consistent with clinical features of mood and bowel disorders including anxiety and abnormal gastrointestinal motility [Holmes, A., Murphy, D.L., Crawley, J.N., 2003. Abnormal behavioral phenotypes of serotonin transporter knockout mice: parallels with human anxiety and depression. Biol. Psychiatry 54, 953-959.]. In the present study, we evaluated bladder function in 5-HTT(-/-) mice. We have found that female 5-HTT(-/-) mice exhibit bladder dysfunction, characterized by significant increases in the frequency of spontaneous non-voiding bladder contractions and decreases in void volume compared to control female mice. These differences were not observed in male knockout mice. These studies provide significant supporting data for a mechanistic link between alterations in 5-HT, depression, IBS and overactive bladder in women.

Animals↗

PubMed2006

Pancreatobiliary afferent recordings in the anaesthetised Australian possum.

The sensory innervation to the pancreatobiliary system is poorly characterized. Afferent signals from the gastrointestinal tract and biliary tree are transmitted to the central nervous system via the vagus and spinal nerves. We aimed to record afferent discharge in order to characterize the vagal and splanchnic afferent signals from the possum upper gastrointestinal tract, biliary tree and pancreas. In 21 anaesthetised possums nerve fibres were teased from the vagus or splanchnic nerve for multi-unit recording. Mechanical stimuli consisted of balloon distension of the gallbladder and duodenum (2-7 ml) and fluid distension (0-20 mm Hg) of the bile or pancreatic ducts. Approximately 60% of fibres from all nerves displayed spontaneous discharge. Spinal afferent responses to mechanical stimuli were infrequent (n=13). Increased discharge occurred in response to duodenal (12/99 fibres) or gallbladder (7/96 fibres) distension, but not to bile duct (0/73 fibres) or pancreatic duct (0/51 fibres) distension. Vagal afferent responses to distension of the duodenum or stomach (5-30 ml) were more common (n=8). Increased discharge was recorded in response to duodenal (49/134 fibres), or gastric (22/70 fibres) distension. Responses to gallbladder distension were less frequent (6/99 fibres) and as with the spinal afferent no response to bile duct (0/66) or pancreatic duct (0/70) distension were recorded. We conclude that mechanosensitive afferents in the pancreatobiliary system are relatively rare, particularly within the ducts, and/or that they are adapted to monitor stimuli other than luminal distension.

Action Potentials↗

PubMed2006

Endocrine correlates of acute nausea and vomiting.

This paper gives an overview of studies investigating endocrine changes in acute nausea and vomiting. The aetiology of nausea and vomiting is not fully understood, but it has been shown that different stress hormones are released into circulation during motion sickness. Studies with animals and humans have shown that acute nausea activates the hypothalamo-pituitary-adrenal axis and the neurohypophyseal system. So-called stress hormones, like adrenocorticotropic hormone, cortisol, and antidiuretic hormone, are released concomitant with nausea and vomiting in motion sickness, but do not seem to be involved in the aetiology of motion sickness. Nevertheless, plasma levels of stress hormones more or less correlate to the intensity of nausea related symptoms. Although gastroenteropancreatic hormones are involved in gastrointestinal motility, there are only few data describing their changes in response to acute nausea or vomiting.

Animals↗

PubMed2006

Postoperative nausea and vomiting.

Nausea and vomiting following surgery may either occur as postoperative nausea and vomiting, which is a condition that is mainly related to anesthesia, or as secondary to postoperative ileus, which denotes inhibition of gastrointestinal motility following surgery. Postoperative ileus is a multifactorial event with several contributing mechanisms. Although postoperative nausea and vomiting pathophysiology has been quite well-studied little is known about it. There are multiple targets for treatment, prevention, and its successful empirical management e.g. by 5-HT(3) receptor antagonists. This review describes different aspects of the pathophysiology of postoperative ileus and postoperative nausea and vomiting, their relevance to postoperative care, and the standardized approach to manage postoperative nausea and vomiting that was established by Apfel and coworkers. Despite the recent advances in the understanding and treatment of conditions that trigger nausea and vomiting in the postoperative period, these symptoms remain a significant problem that affects patients' recovery, comfort, and treatment cost.

Antiemetics↗

PubMed2005

Gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is increasingly common worldwide; symptoms differ between individuals and endoscopically visible injury is present in only about 50% of cases. Although GERD is a disorder of gastrointestinal motility and structure, the most effective therapy is based on the use of acid antisecretory drugs. Proton pump inhibitors (PPIs), the most effective class of acid suppression agents to date, have revolutionised the management of GERD. However, PPIs do have some shortcomings and recent developments include documentation of increased healing rates with more prolonged acid suppression, more prolonged acid suppression with a new PPI (tenatoprazole) and more rapid onset of acid suppression with a new class of drugs, the reversible, potassium-competitive acid blockers. Studies with motility agents, such as the 5-HT(4) partial agonist tegaserod and the GABA(B) agonist baclofen, indicate that motility is important in the pathogenesis of GERD but, for several reasons, it will be a challenge to develop new classes of drug that outperform current PPIs with respect to efficacy, broad applicability and safety.

Animals↗

PubMed2005

Physiology of ghrelin and related peptides.

Growth hormone (GH) released from pituitary under direct control of hypothalamic releasing (i.e., GHRH) and inhibiting (i.e., sst or SRIF) hormones is an anabolic hormone that regulates metabolism of proteins, fats, sugars and minerals in mammals. Cyril Bowers' discovery of GH-releasing peptide (GHRP-6) was followed by a search for synthetic peptide and nonpeptide GH-secretagogues (GHSs) that stimulate GH release, as well as a receptor(s) unique from GHRH receptor. GHRH and GHSs operate through distinct G protein-coupled receptors to release GH. Signal transduction pathways activated by GHS increase intracellular Ca2+ concentration in somatotrophs, whereas GHRH increases cAMP. Isolation and characterization of ghrelin, the natural ligand for GHS receptor, has opened a new era of understanding to physiology of anabolism, feeding behavior, and nutritional homeostasis for GH secretion and gastrointestinal motility through gut-brain interactions. Other peptide hormones (i.e., motilin, TRH, PACAP, GnRH, leptin, FMRF amide, galanin, NPY, NPW) from gut, brain and other tissues also play a role in modulating GH secretion in livestock and lower vertebrate species. Physiological processes, such as neurotransmission, and secretion of hormones or enzymes, require fusion of secretory vesicles at the cell plasma membrane and expulsion of vesicular contents. This process for GH release from porcine somatotrophs was revealed by atomic force microscopy (AFM), transmission electron microscopy (TEM) and immunohistochemical distribution of the cells in pituitary during stages of development.

Amino Acid Sequence↗

PubMed2005

The responses to manipulation of extracellular and intracellular calcium are altered in the streptozotocin-diabetic rat colon and ileum.

Studies were performed to see if alterations in Ca2+ homeostasis underlie the gastrointestinal motility complications seen in many diabetic patients. Experiments were performed on colonic and ileal tissues taken from streptozotocin-induced diabetic and control rats. Diabetes caused alterations in the responses of the tissues to Ca2+ manipulation but these differed between the colon and ileum. In the colon a small but not significant increase in contractile responses to CaCl2 was observed in diabetic tissues, whereas the responses of the ileum were depressed relative to those of the controls. In contrast, responses of the diabetic ileum to the Ca2+ channel agonist Bay K8644 were greater than those of the controls, whilst the agonist failed to contract the colon. Similarly, the Ca2+-ATPase inhibitors, thapsigargin and cyclopiazonic acid, produced contractions which were greater in diabetic ileal tissues. Thus, alterations in the responses of the diabetic gut to Ca2+ manipulation are complex, and also tissue-specific.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2005

Contrasting effects of tetraethylammonium and 4-aminopyridine on the gastrointestinal function of mice.

Many different K+ channels have been identified in the gastrointestinal tract, and the two classical K+ channel blockers, tetraethylammonium and 4-aminopyridine, show different sensitivity for these channels. The aim of the present study was to compare the effects of tetraethylammonium and 4-aminopyridine on the gastrointestinal function of mice. 4-Aminopyridine (5 mg/kg, p.o.) inhibited, but tetraethylammonium (40 mg/kg, p.o.) enhanced, the intestinal propulsion of a charcoal suspension in conscious mice. Studies in vitro showed that perfusion of 5 mM 4-aminopyridine increased the maximal contractile force and minimal relaxation force, and decreased the amplitude and frequency of the peristaltic contraction of the isolated duodenum. However, perfusion of 5 mM tetraethylammonium increased the maximal contractile force, the minimal relaxation force and the amplitude of the contraction. The effects of tetraethylammonium and 4-aminopyridine on the duodenal contraction could be abolished completely by application of 5 microM verapamil. Our results in vivo and in vitro showed that tetraethylammonium and 4-aminopyridine had contrasting effects on the gastrointestinal function of mice.

4-Aminopyridine↗