Biomedical subjects

W J Snape

Publications and source records attributed to W J Snape.

At least 37 records · Page 2Linked to original sources

PubMed1991

Effect of 5-hydroxytryptamine and its antagonists on colonic smooth muscle of the rabbit.

The effect of 5-hydroxytryptamine (5HT) was studied in circular and longitudinal muscle from the proximal and distal colon of New Zealand white rabbits. 5HT stimulated a dose-dependent isometric contraction of distal and proximal circular muscle that was greater than in distal longitudinal muscle (P less than 0.01). 5HT did not stimulate taenia coli longitudinal muscle. The EC50 for 5HT stimulation of distal circular muscle (-7.0 +/- 0.1), distal longitudinal muscle, and proximal circular muscle was similar. Methysergide dose-dependently inhibited the 5HT stimulation of both proximal and distal circular muscle. The IC50 for methysergide inhibition of 5HT (5 x 10(-7) M) stimulation was -5.5 +/- 0.2. Ketanserine and ICS 205-930 did not inhibit 5HT stimulation of colonic muscle. Tetrodotoxin (TTX) decreased the potency, but not the efficacy of 5HT stimulation of proximal and distal circular muscle. Atropine decreased the potency (EC50 = -6.6 +/- 0.1) (P less than 0.05) and the efficacy by 40%. Electrical field stimulation (EFS) caused an on-contraction and off-contraction of distal circular muscle and an on-contraction of proximal circular muscle. 5HT decreased the off-contraction of the distal circular muscle but did not affect the on-contraction of the other muscle strips. 5HT receptor antagonists did not affect EFS of the tissue. The studies suggest: (1) 5HT stimulates circular colonic muscle with greater efficacy than longitudinal muscle, (2) 5HT stimulates circular muscle through a 5HT1 receptor, (3) there is atropine-sensitive and atropine-insensitive 5HT stimulation of circular colonic muscle, (4) 5HT inhibits neurons responsible for the off-contraction in distal circular muscle without affecting the on-contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

U.S. experience with omeprazole in duodenal ulcer. Multicenter double-blind comparative study with ranitidine. The Omeprazole DU Comparative Study Group.

To assess the comparative efficacy of omeprazole 20 mg, a proton pump inhibitor, versus ranitidine 150 mg twice a day, an H2-receptor antagonist, in healing duodenal ulcers we performed a randomized, double-blind, multicenter trial in 309 patients with endoscopically diagnosed ulcers. Patients were treated for up to four weeks and were seen at week 2 and at week 4, if unhealed at week 2, for determination of ulcer status by endoscopy, review of daily self-assessment symptom diaries, and clinical laboratory including fasting serum gastrin. Gastrin levels were repeated two weeks after cessation of study medication. Evaluation of baseline demographic and laboratory parameters demonstrated no significant differences between the two groups at entry. At week 2, 42% of the omeprazole and 34% of the ranitidine-treated patients were healed (P = NS). At week 4, there was a 19% advantage in ulcer healing for the omeprazole-treated patients in comparison to those treated with ranitidine (82% vs 63%, respectively, P less than 0.05). Healing of ulcers greater than or equal to 1.0 cm occurred in 83% of those treated with omeprazole versus 37% treated with ranitidine (P less than 0.01). There were no significant differences in rate of pain relief or incidence of clinical laboratory abnormalities. Mean fasting serum gastrin value during treatment increased over the baseline in both groups, (P less than 0.05). The percent change was significantly greater with omeprazole but few patients had elevations above the upper limit of normal for the assay. Both drugs were well tolerated. Omeprazole 20 mg demonstrated superiority in healing duodenal ulcers at four weeks in comparison to ranitidine 150 mg twice daily and was more effective in healing ulcers greater than or equal to 1.0 cm.

Double-Blind Method↗

PubMed1991

Colonic motility and transit in health and ulcerative colitis.

Preprandial and postprandial colonic motility and transit (scintigraphy), with respect to the splenic flexure, were studied in 10 patients with ulcerative colitis and in 9 healthy subjects. The healthy subjects had a postprandial increase in intraluminal pressure that was significantly (P less than 0.03) greater in the descending colon than in other regions of the colon. In ulcerative colitis, the pressure was decreased in all regions compared with healthy subjects, with no significant pressure gradient among different regions. In normal subjects, transit was quiescent during fasting; eating stimulated both antegrade and retrograde transit. In ulcerative colitis, transit was variable before as well as after the meal. Both healthy subjects and patients with ulcerative colitis had more rapid emptying from the splenic flexure into the sigmoid than into the transverse colon. More frequent, low-amplitude, postprandial propagating contractions occurred in ulcerative colitis (P less than 0.05) than in healthy subjects. Propagating contractions were always antegrade and caused a rapid movement of the tracer into the sigmoid. In conclusion, ulcerative colitis is characterized by (a) decreased contractility, (b) increased low-amplitude propagating contractions, and (c) variable transit. These disturbances may accentuate the diarrhea in ulcerative colitis.

Adult↗

PubMed1991

Effect of eating on colonic motility and transit in patients with functional diarrhea. Simultaneous scintigraphic and manometric evaluations.

The aim of this study was to correlate colonic motility with transit in 8 patients with functional diarrhea compared to 12 healthy subjects. Intraluminal pressure was measured with perfused catheter ports in the transverse colon, splenic flexure, and descending and sigmoid colons. Transit of the luminal contents was measured by following the movement of 99mTC-diethylenetriaminepentaacetic acid instilled as a bolus in the splenic flexure. In patients with diarrhea, the intraluminal marker moved in and out of the transverse and sigmoid colon regions of interest during fasting, unlike healthy subjects, in whom the marker remained in the splenic flexure. After eating, radioactivity immediately increased in both the transverse and sigmoid colons in healthy subjects. In the patients with diarrhea, eating did not alter the marker movement into the different regions of the colon compared with fasting. Within 100 minutes of eating, the intraluminal marker almost disappeared from the regions of interest in patients with diarrhea. Postprandial colonic nonpropagating contractions increased in each region of the colon in healthy subjects; there was only a small postprandial increase in colonic motility in patients with diarrhea. However, the numbers of fasting and postprandial propagating contractions were increased in patients with diarrhea compared with healthy subjects (P less than 0.02). Each propagating contraction moved more tracer in patients with diarrhea than in healthy subjects (P less than 0.05). These studies suggest that (a) in patients with diarrhea, the fluctuation of marker in both transverse and sigmoid colons during the fasting and postprandial periods is associated with decreased nonsegmenting contractions and frequent propagating contractions; and (b) in healthy subjects, the intraluminal marker moved after eating because of a pressure gradient caused by nonpropagating contractions.

Adult↗

PubMed1991

Perinatal changes in bombesin-stimulated muscle contraction in rabbit stomach and colon.

Bombesin and its mammalian homologue, gastrin-releasing peptide, stimulate smooth muscle contraction and may promote the growth of gastrointestinal tissues. Isometric contraction of strips from circular muscle of the gastric fundus and longitudinal muscle of the distal colon were used to compare changes in the response to bombesin in newborn and weanling rabbits. There was an age-related qualitative change in gastric muscle from biphasic contractions including phasic and tonic components in the newborn to phasic contractions alone in the weanling. The colon contractions were tonic at both ages. In both tissues there was an age-related fivefold increase in stress in response to maximally effective concentrations of bethanechol (P less than 0.05). In contrast, in the stomach age-related decreases in the response to maximally effective concentrations of bombesin were observed, from 2930 +/- 179 mN/cm2 (98% of the maximal response to bethanechol) in the newborn to 565 +/- 81 mN/cm2 (4% of the maximal response to bethanechol) in the weanling (P less than 0.005). In the colon, a twofold increase in response to bombesin was observed, from 446 +/- 59 mN/cm2 (82% of the response to bethanechol) in the newborn to 862 +/- 11 mN/cm2 (29% of the response to bethanechol) in the weanling (P less than 0.05). No age-related changes were observed in the potency of bombesin in either tissue. Neither atropine nor tetrodotoxin altered the contractions in either tissue, suggesting that bombesin interacted directly with myocytes. There was three times as much bombesinlike immunoreactivity in the stomach compared with the colon, but no age-related changes in either tissue. In summary, by the age of weanling the stomach lost the tonic component of contraction and 80% of the efficacy of bombesin-stimulated phasic contraction that had been present in the newborn. The loss of efficacy, absolute in the stomach and relative to bethanechol in the colon, suggest that bombesin may be most important in stimulating motility in the neonatal period.

Animals↗

PubMed1991

Anatomic contribution to differences in rabbit colonic muscle contraction.

The aim of this study was to determine if differences in the force of contraction in different regions of the rabbit colon are associated with variations in the histology of the corresponding muscle tissues. Circular and longitudinal muscles were isolated from strips of proximal and distal colonic muscle. Muscle strips stretched to L0 were either stimulated to contract or were processed for electron microscopy. Cross-sections of the smooth muscle cells of the taenia coli had a larger perimeter (P less than 0.001) and were surrounded by increased extracellular matrix (28% of the standardized box) compared with the muscle cells from the other sites in the colon (7%-13%) (P less than 0.001). Cross-sections of the proximal circular muscle cells had a smaller perimeter and were present in a greater number than the cells from other areas of the colon. The distal circular muscle generated a larger force than the other muscles after stimulation with bethanechol or K+ (P less than 0.05). The taenia developed less force than the other muscles (P less than 0.05). Bethanechol was a less potent stimulant for the longitudinal muscles than for the circular muscles (P less than 0.05). This study suggests that (1) the decreased efficacy of bethanechol and K+ stimulation of the taenia coli is caused in part by the smaller number of cells that are available to contract and (2) the increased efficacy for the stimulation of the distal circular muscle compared with the proximal circular muscle is unrelated to the mass of muscle and seems to be related to an inherent property of the muscle.

Animals↗

PubMed1991

Defect in colonic smooth muscle contraction in patients with ulcerative colitis.

Patients with ulcerative colitis have decreased postprandial colonic contractions. The purpose of this study was to determine whether the smooth muscle from patients with ulcerative colitis responds abnormally in vitro to different stimuli. Circular colonic smooth muscle strips from patients with ulcerative colitis, acute diverticular disease, or adenocarcinoma were stretched to the optimal length and stimulated with electrical field stimulation (EFS), bethanechol, or increased concentrations of extracellular K+. The EFS-stimulated on-contraction was similar in each group, but the off-contraction was decreased in patients with colitis compared with patients with cancer (P less than 0.02) or diverticular disease (P less than 0.01). Bethanechol stimulated a dose-dependent colonic contraction, which was less in the strips from patients with colitis compared with cancer (P less than 0.02) or diverticular disease (P less than 0.05). The response to increased extracellular K+ was less in muscle from patients with colitis (P less than 0.01) than in the other tissues. Muscle from diverticular disease developed greater stress to K+ stimulation than did muscle from cancer (P less than 0.05). These studies suggest that there is a decrease in the force of muscle contraction in colonic muscle obtained from patients with colitis compared with normal muscle resected from patients with cancer or with muscle associated with diverticular disease of the colon. The similar relatively low amplitude of the on-contraction in each group suggests the physiological release of an inhibitory neurotransmitter.

Adenocarcinoma↗

PubMed1991

Developmental changes in agonist-mediated colonic smooth muscle contraction in the rabbit.

We studied smooth muscle strips from rabbit distal colon to determine age-related changes in length-tension properties and agonist-mediated contraction. Strips from newborn (1-d-old) and weanling (11-wk-old) rabbits were oriented to measure isometric tension in longitudinal muscle. Active tension comprised 47 +/- 4 and 75 +/- 5% of the total tension in the newborn and weanling, respectively. Total and active tensions in the weanling were greater than in the newborn (p less than 0.001). Although the potencies for bethanechol were similar, the maximal response was nearly 9-fold greater in weanlings (6900 +/- 292 mN/cm2) versus newborns (753 +/- 112 mN/cm2), p less than 0.001. Maximal stress increased with age for bethanechol, high extracellular potassium, substance P, neurokinin A, cholecystokinin octapeptide, bombesin, and serotonin. ED50 for bethanechol, substance P, neurokinin A, and bombesin did not change with age. Serotonin was 12 times more potent in newborns versus weanlings (p less than 0.05). In contrast, cholecystokinin octapeptide was five times less potent in newborns (18.6 nM versus 3.4 nM, respectively, p less than 0.05). Substance P-induced contractions were inhibited partially by atropine. We conclude that length-tension properties of longitudinal colonic smooth muscle differ, and responses to agonists increase with age.

Animals↗

PubMed1991

Active idiopathic ulcerative colitis in a patient with ongoing HIV-related immunodepression.

It is suspected that immune mechanisms are important in the pathogenesis of ulcerative colitis. The following is a case report of a patient with human immunodeficiency virus-related immunodeficiency whose ulcerative colitis ran a course independent of the depression of his peripheral CD4 cells. Thus, peripheral CD4 cells may have little role in the pathogenesis of ulcerative colitis.

Adult↗

PubMed1991

The role of a colonic motility disturbance in ulcerative colitis.

Alterations in colonic motility appear to exacerbate the symptom of increased frequency of bowel movements in patients with ulcerative colitis. Decreased segmenting contractions allow rapid forward movement of luminal contents accentuating the diarrhea. The decrease in segmenting colonic motility is further exacerbated by increased numbers of propagating contractions. The rapid transport of intraluminal contents with a propagating contractions into a nondistensible rectum may be one explanation for the relative high incidence of fecal incontinence in these patients. The pathogenesis of the decreased segmenting contractions appears due to an electromechanical dissociation resulting from inhibition of myosin light chain phosphorylation. It is possible that several inflammatory mediators including free oxygen radicals decrease smooth muscle cell function.

Animals↗

PubMed1990

Postprandial colonic transit and motor activity in chronic constipation.

The aim of this study was to correlate colonic motility and transit in patients with constipation and symptoms of the irritable bowel syndrome. Studies were performed in 16 patients with constipation and compared with the results in 12 healthy subjects. Intraluminal pressure was measured with perfused catheter ports in the transverse colon, splenic flexure, and descending and sigmoid colon. Movement of the luminal contents was measured by following the movement of Technetium-99m-DTPA that was instilled as a bolus in the splenic flexure. In both healthy subjects and patients with constipation there was no movement of the intraluminal tracer and no increase in intraluminal pressure during fasting. After eating a meal, healthy subjects and one group of the constipated patients had an increase in the radioactive marker in the transverse colon (p less than 0.03) and in the sigmoid colon (p less than 0.03). The movement of the intraluminal contents was associated with a positive pressure gradient between the descending colon and the transverse and sigmoid colon. There was no retrograde movement of the intraluminal contents and no postprandial increase in intraluminal pressure in the second group of patients with constipation. In healthy subjects, propagating contractions, which were associated with the rapid movement of intraluminal contents, began 60 min after eating. There were no propagating contractions in patients with constipation. These studies suggest that (a) the movement of intraluminal contents in healthy and constipated patients is determined by the postprandial pressure gradients within the colon, and (b) the propagating contraction is necessary for a normal bowel habit.

Adult↗

PubMed1990

The activation of calcium and calcium-activated potassium channels in mammalian colonic smooth muscle by substance P.

1. The regulation of Ca2(+)-activated K+ channels by the agonist substance P in freshly dissociated smooth muscle cells from the rabbit longitudinal colonic muscle was characterized using the patch clamp technique. 2. In the cell-attached recording mode, when pipette and bath solutions contained equal [K+] (126 mM), the Ca2(+)-activated K+ channels showed a linear current-voltage relationship (between -50 mV and 50 mV) with a slope conductance of 210 +/- 35 pS (n = 12). Reversal potential measurements indicated that the channel was highly selective for K+ over Na+ (PK/PNa = 110). 3. Channels were activated by depolarizing membrane voltages and cytosolic Ca2+, and in inside-out patches channel activation depended sigmoidally on voltage and [Ca2+]. The potential for half-activation at a cytosolic [Ca2+] of 5 x 10(-6) M was 0 mV. A tenfold increase in cytosolic Ca2+ resulted in a 60 mV shift of the sigmoidal voltage activation curve to more negative potentials. 4. Threshold concentrations of substance P (10(-12) M), which did not result in cell contraction, caused a prolonged activation of K+ channels. The K+ channels were observed to open in clusters: simultaneous opening of multiple channels was interrupted by complete, prolonged channel closure. 5. Lowering bath [Ca2+] to submicromolar concentrations abolished the effect of substance P. The activation of K+ channels by substance P (10(-12) M) was also inhibited by the dihydropyridine nifedipine (10(-6) M), a blocker of L-type Ca2+ channels. 6. In the whole-cell recording mode, with the pipette solution containing 126 mM-KCl, 0.77 mM-EGTA and 1 mM-ATP, depolarization from a holding potential of -70 mV elicited outward currents which increased to steady-state values. These were K+ currents as they were blocked by TEA (tetraethylammonium, 30 mM) and Ba2+ (1 mM) and were abolished when pipette K+ was replaced by Cs+. 7. The depolarization-activated outward current was not affected by lowering extracellular [Ca2+] or by the Ca2+ channel antagonists Cd2+ (200 microM), nifedipine (10(-6)-10(-5) M) or verapamil (10(-6) M). The current was greatly reduced when the EGTA concentration in the pipette solution was increased from 0.77 to 10 mM. 8. When the pipette solution contained CsCl, membrane depolarization activated inward currents. The peak inward current was identified as current through L-type Ca2+ channels based on its voltage- and time-dependent kinetics, and its modulation by dihydropyridines.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Neurokinin inhibition of cholinergic myenteric neurons in canine antrum.

Neurokinins regulate gastrointestinal motility by interacting with receptors on both muscle layers and on myenteric plexus neurons. To determine if specific neurokinin (NK) receptor agonists can mediate inhibitory effects on myenteric neurons, we studied the effect of the NK-1 agonist substance P methylester (SPME) and the putative endogenous NK-2 receptor ligand neurokinin A (NKA) on [3H]acetylcholine [( 3H]ACh) release induced by electrical field stimulation from muscle strips cut from the canine gastric antrum. SPME but not NKA caused a dose-dependent inhibition of stimulated [3H]ACh release in tissues containing the myenteric plexus. The inhibition was not seen in longitudinal muscle without myenteric plexus. Pretreatment of tissues with indomethacin or antiserum to vasoactive intestinal polypeptide (VIP) but not naloxone or adrenergic or cholingergic blockade abolished the SPME-induced inhibition. Exogenous VIP stimulated the release of prostaglandin E2 (PGE2) from full thickness strips, and both VIP and PGE2 inhibited [3H]ACh release induced by electrical depolarization. These findings suggest that NK-1 receptor agonists can selectively inhibit stimulated [3H]ACh release and that this inhibition may involve the release of VIP and PGE2 from neurons within the myenteric plexus.

Acetylcholine↗

PubMed1990

Substance P and CGRP mediate motor response of rabbit colon to capsaicin.

Primary afferent nerve terminals located in the mammalian gut wall may play a role in region-specific modulation of gastrointestinal motility. In the present study, we sought to characterize the effect of neuropeptides released from these afferents by capsaicin (CAP) on contractile activity of smooth muscle from the distal rabbit colon. CAP caused a release of acetylcholine and immunoreactivity for substance P (SP) and calcitonin gene-related peptide (CGRP) from the muscle coat. CAP caused a dose-dependent transient stimulation of longitudinal muscle contractions, followed by prolonged inhibition of spontaneous but not stimulated contractile activity. The initial stimulation was abolished by the SP antagonist spantide and by atropine. The inhibitory effect was reduced by repeated exposure of muscle to CGRP. The effect of CGRP on spontaneous contractions differed between longitudinal and circular muscle. In longitudinal muscle, a stimulation was preceded by a transient inhibition, whereas in circular muscle, only inhibition was seen. Both effects were resistant to tetrodotoxin. Repeated exposure of circular but not longitudinal muscle to CGRP resulted in a disappearance of the peptide's inhibitory effect. Exogenously applied CGRP was only a weak antagonist of contractions stimulated by SP and bethanechol. These findings suggest that in the rabbit colon at least the following two neuropeptides are released from CAP-sensitive nerve fibers: a neurokinin peptide from nerve terminals located within the myenteric plexus and CGRP from terminals probably located within the circular muscle layer.

Acetylcholine↗

PubMed1989

Differences in the response of proximal and distal rabbit colonic muscle after electrical field stimulation.

Electrical field stimulation (EFS) was performed on rabbit proximal and distal circular colonic smooth muscle to study the mechanisms of neural control of the colon. Electrical pulses were applied with parallel silver plate electrodes to muscle that had been stretched to Lo. The proximal muscle demonstrated an on-contraction during EFS. In distal muscle, EFS initiated an on-relaxation, followed by an on-contraction and an off-contraction. The time delay for the on-contraction of distal muscle was longer by 2.5 +/- 0.5 s than was the delay in proximal muscle (p less than 0.02). The amplitudes of the on- and off-contraction were dependent on the frequency of the EFS. The on- and off-responses were completely inhibited by 3 x 10(-6) M tetrodotoxin. Atropine inhibited the distal on-contraction at all EFS frequencies and the proximal on-response at EFS frequencies less than 16 Hz. Atropine had a partial inhibitory effect on the distal off-response (approximately 30%). Bombesin and substance P were released during prolonged EFS. Desensitization of the distal colonic muscle to bombesin did not affect the distal off-contraction. However, desensitization of the tissue to substance P and exposure to substance P antagonists inhibited the distal off-contraction. These studies suggest that (a) acetylcholine mediates the on-contraction of the distal circular colonic muscle, and a major part of the on-contraction for the proximal muscle, and (b) substance P is responsible for the off-contraction of the distal muscle.

Animals↗

PubMed1989

Involvement of substance P in noncholinergic excitation of rabbit colonic muscle.

Neurokinins have been implicated as noncholinergic excitatory neurotransmitters in the mammalian gastrointestinal tract. To characterize the myogenic and neurogenic response of colonic muscle to neurokinins we studied the mechanical response of muscle strips from proximal and distal colon and the release of [3H]acetylcholine in response to substance P (SP), neurokinin A (NKA) and neurokinin B (NKB). All neurokinins caused a dose-dependent inotropic response. SP was 80 times more potent in distal compared with proximal longitudinal muscle. The rank order of potencies in proximal longitudinal muscle was NKA greater than SP = NKB and in distal muscle NKA = SP = NKB. Desensitization to SP or pretreatment with a SP antagonist inhibited the mechanical response to SP and the atropine-resistant inotropic off response to electrical stimulation. Only longitudinal muscle from distal colon had an atropine- and hexamethonium-sensitive inotropic component to SP. In contrast, all three peptides were equipotent in releasing [3H]acetylcholine from longitudinal muscle strips preincubated with [3H]choline. These results suggest the following: 1) SP is a potent agonist of rabbit colon with a proximal distal gradient in biological potency; 2) the myogenic response of the distal colon appears to be mediated through a NK-1 receptor; and 3) SP is a major mediator of the noncholinergic component of the off response in distal longitudinal muscle.

Acetylcholine↗

PubMed1989

Development of calcium channels in gastric smooth muscle.

We used [3H]nitrendipine to characterize dihydropyridine sensitive calcium channels on cells isolated from neonatal (1 d) and weanling (11 wk) rabbit gastric fundic and antral smooth muscle. Incubating with and without nifedipine 20 microM, specific binding was 56 +/- 4% of total binding at 0.1 nM [3H]nitrendipine. Specific binding was saturable, reversible, achieved equilibrium by 10 min at 4 degrees C, and was linearly related to cell concentration. The affinity constant for [3H]nitrendipine was higher in weanling fundus (kd = 243 +/- 121 pM) versus antrum (kd = 771 +/- 190 pM), p less than 0.05. There were no age-related changes in affinity. In the antrum, the number of binding sites (Bmax) increased from 6,000 +/- 266/cell in neonates to 27,500 +/- 8,440/cell in weanlings (p less than 0.05). In the fundus Bmax was 7,750 +/- 2,100/cell in neonates, and there was no age-related change. To assess function, we compared isometric stress in full thickness muscle strips oriented to the circular layer. Bethanechol stimulated dose-dependent tonic contractions in the fundus and phasic contractions in the antrum. Maximal stress increased with age from 305 +/- 54 mN/cm2 to 1140 +/- 73 mN/cm2 (p less than 0.05) in the fundus and from 72 +/- 20 mN/cm2 to 154 +/- 30 mN/cm2 (p less than 0.05) in the antrum. Preincubation and incubation without calcium resulted in reversible inhibition of contraction at both ages. Nifedipine 10-microM inhibited 100% of bethanechol-stimulated contraction in the antrum, but only 25% in the fundus at both ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Developmental changes in agonist-mediated gastric smooth muscle contraction in the rabbit.

We studied smooth muscle strips from rabbit proximal stomach to explore the age-related changes in agonist-mediated contraction. Strips from neonatal (1 d) and weanling (11 wk) rabbits were oriented to measure isometric tension in circular muscle. Bethanechol stimulated maximal tension in both age groups. Although the potencies for bethanechol were similar (ED50 approximately 5 microM), the maximal response was nearly 4-fold greater in weanling (1140 +/- 73 mN/cm2) versus neonate (305 +/- 54 mN/cm2), p less than 0.001. Maximum stress increased with age for bethanechol, high extracellular K+, and substance P, but not for serotonin, cholecystokinin octapeptide, neurotensin, or bombesin. Only bombesin stimulated larger contraction in neonates (152 +/- 37 mN/cm2) versus weanlings (86 +/- 20 mN/cm2), p less than 0.05. Potencies did not change with age, except for substance P and serotonin. Substance P and serotonin induced early phasic and prolonged tonic contractions, which were unaffected by tetrodotoxin or atropine. ED50 for the phasic and tonic components of substance P-stimulated contraction in neonates were 1.8 and 7.7 nM. Substance P was 60-70 times more potent in neonates versus weanlings (p less than 0.001). ED50 for serotonin-stimulated contraction in neonates (33 and 22 nM, respectively) were 20-30 times more potent than in weanlings (p less than 0.05). Motilin, morphine, epidermal growth factor, and gastrin did not stimulate contraction at either age. We conclude that age-dependent changes in agonist potency and efficacy may be one factor to explain in part the changes that occur in gastric motility during postnatal development.

Animals↗