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Biomedical subjects

W J Snape

Publications and source records attributed to W J Snape.

At least 73 records · Page 4Linked to original sources
PubMed1986

Effect of acute experimental colitis on rabbit colonic smooth muscle.

The membrane potential and contractile activity of colonic circular smooth muscle from New Zealand White rabbits were studied after the production of acute experimental colitis. Colitis was induced in the distal colon by rectal infusion of formaldehyde solution, followed by an intravenous bolus of soluble immune complexes. Despite active mucosal inflammation, there are only occasional inflammatory cells in the muscularis. Electrophysiological studies on tissue from control rabbits and rabbits with colitis were performed using double sucrose gap and intracellular microelectrode techniques. The resting membrane potential was lower (-44 +/- 3 mV) in muscle from rabbits with colitis compared with control animals (-54 +/- 2 mV) (P less than 0.02). Amplitude of the electrotonic potential after a hyperpolarizing current pulse was decreased (P less than 0.05) and the time constant was shortened (P less than 0.01) in muscle from animals with colitis compared with normal animals. Amplitude (13.1 +/- 2.3 mV) and maximum rate of rise (0.24 +/- 0.06 V/s) of the spike potential, initiated by a depolarizing current pulse, were decreased in muscle from animals with colitis compared with muscle from healthy animals (P less than 0.001). Isometric tension generation after electrical and chemical depolarization of the membrane or bethanechol administration was decreased (P less than 0.001) in muscle from colitic animals. These studies suggest 1) membrane resistance and membrane potential are decreased in muscle strips from animals with colitis; and 2) there is a disturbance in the electrical and mechanical response of these tissues after stimulation.

Action Potentials↗
PubMed1985

Comparison of intraluminal and intravenous mediators of colonic response to eating.

Eating a 1000-kcal mixed meal stimulates an increase in distal colonic motility. Fat is the dietary component which is the major stimulant of colonic spike activity. In this study the colonic spike activity increased similarly after the mixed meal [19.1 +/- 2.4 spike potentials (SP)/30 min] and after the fat meal (19.4 +/- 5.4 SP/30 min). Fat stimulated a concentration-dependent increase in colonic motility only when in contact with the gastroduodenal mucosa. Intravenous administration of Liposyn (100 kcal/hr) did not stimulate an increase in colonic spike activity (3.3 +/- 1.3 SP/30 min) despite greater increase in plasma total fatty acid levels than after the oral ingestion of fat. In contrast both the oral ingestion and the intravenous administration of an amino acid mixture (Aminosyn) inhibited the gastrocolonic response after the 1000-kcal mixed meal. Thus, these studies demonstrate: (1) fat stimulates colonic motility only through direct mucosal contact, and (2) a mixture of amino acid inhibits colonic motility through either mucosal contact or by circulating in the plasma. The exact neurohumoral mechanisms involved in both of these effects is unknown at present.

Action Potentials↗
PubMed1985

Increased colonic motility during exposure to a stressful situation.

Colonic smooth muscle spike potentials and contractility were recorded during the periods of stress by a bipolar electrode-perfused catheter apparatus placed in the rectosigmoid colon. Healthy subjects and patients with the irritable colon syndrome (ICS) were exposed to three standardized stressful conditions: (1) ice-water immersion, (2) Stroop stimulus differentiation test, and (3) ball sorting. In healthy controls, colonic motility increased after the first exposure to ice-water immersion (P less than 0.05), Stroop test (P less than 0.05), or ball sorting. Respiratory frequency also increased after exposure to the stressful stimuli. However, repeat exposures to the stress tests did not stimulate colonic motility. An increase in colonic motility occurred in patients with the irritable colon syndrome pretreated with a placebo after exposure to ice water (P less than 0.05), Stroop Test, or ball sorting (P less than 0.05). However, after exposure to the stressful situations patients pretreated with chlordiazepoxide had a diminished increase in colonic motility or in respiratory frequency. These studies suggest: (1) in healthy controls habituation reduces the stress-related increase in colonic motility, and (2) in patients with the irritable colon syndrome, chlordiazepoxide decreases the stress-related increase in colonic motility.

Action Potentials↗
PubMed1985

Role of sodium or calcium in electrical depolarization of feline colonic smooth muscle.

The aim of this study was to compare the role of Na+ and Ca2+ on the membrane potential and contraction of feline colonic circular smooth muscle. The changes in membrane potential were correlated with a change in tension using the double-sucrose gap technique. The estimated resting potential was -62.8 +/- 2.6 mV. A depolarizing current, passed during quiescent periods of the membrane, stimulated a spike potential and caused a concomitant increase in smooth muscle tension. The maximum depolarization rate of the active spike potential was rapid (580 +/- 75 mV/s) and unaffected by the amplitude of the depolarizing current. Reduction of extracellular calcium (0.0 mM Ca2+ plus 5 mM EGTA) or blockade of the calcium channels with verapamil (10(-6)M) slowed the maximum rate of membrane depolarization to 128 +/- 20 mV/s (P less than 0.001). The steady-state amplitude of the electrotonic potential and time constant also decreased in low-calcium solutions. The amplitude of smooth muscle contraction and the time between stimulus and onset of contraction were dependent on the amplitude of the depolarizing current and the concentration of extracellular calcium. Removal of sodium had no effect on the electrotonic potentials, maximum dV/dt of the spike, or the contraction of the smooth muscle. These studies suggest calcium plays a major role in the generation of an active spike potential, colonic smooth muscle contraction requires extracellular calcium and is associated with an active regenerative spike potential, and sodium plays a minor role in the generation of an active spike potential and in the initiation of a contraction in feline colonic smooth muscle.

Action Potentials↗
PubMed1985

Effect of amino acids on isolated colonic smooth muscle from the rabbit.

The purpose of these studies was to evaluate the direct effect of amino acids on rabbit colonic smooth muscle. Isometric tension was measured in circular smooth muscle from the distal colon after the administration of 19 individual L-amino acids. L-Alanine, L-cysteine, L-serine and L-methionine stimulated a dose-dependent increase in isometric tension. The lowest concentration which increased tension of the tissue for each of these amino acids was between 1 X 10(-4) to 5 X 10(-4) M. At a concentration of 10(-3) M, each of these four amino acids stimulated smooth muscle to 40 to 60% of the maximum response to bethanechol (2050 +/- 105 mN/m2). The 15 other amino acids tested had less effect on the colonic smooth muscle. The smooth muscle response to the D-amino acids, D-alanine, D-cysteine or D-serine, was shifted 10-fold to the right. Neural blockade by tetrodotoxin, the alpha adrenergic receptor antagonist, phentolamine, or the alpha-2 antagonist, yohimbine, increased smooth muscle tension, but did not inhibit L-amino acid stimulation of the tissue. Atropine, naloxone or prazosin (alpha-1 adrenergic antagonist) had no effect on amino acid stimulation of the muscle. These data suggest that L-amino acids, alanine, serine, cysteine and methionine stimulate contraction of colonic circular smooth muscle, this response is stereospecific and amino acids appear to stimulate the smooth muscle directly and not through an effect on the myenteric neurons.

Amino Acids↗
PubMed1985

Electrical activity and motility in the isoperistaltic side to side ileal reservoir.

In ten rabbits, electrical activity and motility were measured in a side to side isoperistaltic ileal reservoir of 10 centimeters up to three months postoperatively and compared with normal ileum in three rabbits in the control group. Synchronous short spike wave complexes appeared across the reservoir anastomosis early postoperatively; however, they were not associated with propulsive peristaltic waves. Long intense spike wave complexes were associated with propulsive peristaltic waves in the rabbit ileum. These complexes appeared within two weeks postoperatively; however, they were initially asynchronous across the anastomosis. Within three months postoperatively, these complexes became synchronous across the anastomosis, indicating near normal propulsive function in the reservoir.

Action Potentials↗
PubMed1984

Myoelectric and motor activity of the colon in normal and abnormal states.

The nature of colonic motility in normal subjects is discussed. Colonic myoelectrical control is disturbed in certain diseases: slow-wave activity may be affected, or the postprandial gastrocolonic spike response may be altered. Due to these changes in contractile activity, abnormal movement of materials through the colon takes place. These phenomena are reviewed with reference to the irritable colon syndrome, idiopathic constipation, diverticular disease, diabetes mellitus, peripheral systemic sclerosis, and chronic idiopathic intestinal pseudo-obstruction. The treatment of hypermotile states requires the use of agents that diminish colonic motility. If the colon is inert, however, stimulating drugs, e.g. metoclopramide or prostigmine, are indicated.

Colon↗
PubMed1983

Neurohumoral control of colonic motility in the rabbit.

Colonic motility was examined in the proximal (taeniated) and distal (nontaeniated) colon of New Zealand White rabbits. Colonic myoelectric and contractile activities were recorded by bipolar electrodes and extraluminal strain gauges sewn on the antimesenteric serosal surface of the proximal and distal colon. Slow-wave frequency consistently was slower in the proximal colon (13.2 +/- 0.9) compared with the distal colon (15.8 +/- 1.2) (P less than 0.05). During the control period 81.8 +/- 5.2% of slow waves have superimposed spike potentials in the proximal colon. The distal colon had similar amounts of spike activity. The distal colon had increased base-line contractility (P less than 0.02). Atropine inhibited spike and contractile activity on both sides of the colon, but the distal colon still had more contractile activity than the proximal colon (P less than 0.02). The alpha-adrenergic agonist phenylephrine and antagonist phentolamine had no effect on colonic motility. Isoproterenol inhibited colonic smooth muscle spike and contractile activity. This effect was blocked by propranolol. Administration of trimethaphan camsylate caused an increase in spike and contractile activity only in the distal colon. The effect of trimethaphan on the distal colon was inhibited by atropine. These studies show that 1) tonic cholinergic stimulation exists both in the proximal and in the distal colon, 2) circulating catecholamines have minimal effect on base-line colonic motility, and 3) tonic nonadrenergic inhibition of the distal colon modulates the tonic cholinergic stimulation.

Animals↗
PubMed1983

Role of cholecystokinin in the gastrocolonic response to a fat meal.

The fat component of the meal is the major stimulant of the gastrocolonic response. The aim of this study was to characterize the mechanism of the gastrocolonic response after eating fat in healthy human volunteers. A bipolar clip electrode recorded spike activity (SP) from the distal colon. An immediate increase in colonic spike activity occurred after eating a fat meal (18.0 +/- 3.0 SP/30 min) (p less than 0.02). Spike activity remained elevated for 90 min after eating the fat meal (18.6 +/- 2.7 SP/30 min) (p less than 0.01). The intravenous infusion of naloxone or atropine inhibited the fat-induced increase in colonic motility. Cholecystokinin is a candidate mediator of the fat-stimulated gastrocolonic response. The intravenous infusion of the octapeptide of cholecystokinin (20 ng/kg . h) stimulated an increase in distal colonic spike activity (16.0 +/- 3.7 SP/30 min) (p less than 0.025). Intravenous atropine did not affect stimulation of colonic motility by the octapeptide of cholecystokinin. Continuous infusion of naloxone, however, did inhibit stimulation of colonic spike activity by the octapeptide of cholecystokinin. There was no cross-reactivity between opiate or muscarinic receptors. These data suggest (a) fat stimulation of the gastro-colonic response required a muscarinic and opiate receptor, and (b) octapeptide of cholecystokinin can stimulate colonic motility, but it is not the major mediator of the gastrocolonic response.

Adult↗
PubMed1982

Effect of calcium on neurohumoral stimulation of feline colonic smooth muscle.

The purpose of this study was to compare the effect of altering the extracellular calcium ion concentration on bethanechol or octapeptide of cholecystokinin (OP-CCK) stimulation of the isolated transverse colon of the cat. Myoelectric activity was recorded with monopolar glass-pore electrodes. Bethanechol (10(-6) M) stimulated an increase in the number of slow waves with superimposed spike potentials to 85.5 +/- 5.3% (P less than 0.001) compared with the basal spike activity (8.9 +/- 1.4%). OP-CCK (4 x 10(-9)) also increased spike activity (80.7 +/- 3.8%, P less than 0.001), which was not inhibited by atropine, phentolamine, or propranolol. Addition of 0.0 mM calcium solution to the colonic smooth muscle abolished both slow-wave and spike activity, which returned after replacing 0.25 mM calcium in the solution. Bethanechol stimulated a greater increase in spike activity as the concentration of calcium was increased. OP-CCK stimulation of colonic spike activity was more sensitive to the extracellular calcium concentration than bethanechol stimulation. Verapamil had a minimal effect on bethanechol stimulation of colonic spike activity, but it inhibited the OP-CCK stimulation. These studies suggest that 1) OP-CCK appears to stimulate colonic smooth muscle directly and 2) OP-CCK requires the presence of a greater amount of extracellular ionic calcium in order to stimulate colonic spike activity compared with bethanechol.

Animals↗
PubMed1982

Characterization of opiate-mediated responses of the feline ileum and ileocecal sphincter.

Although opioid peptides have been demonstrated immunohistochemically in the feline intestine, the action of these peptides is unknown. The aims of this study were: (a) to determine the distal ileal and ileocecal sphincter (ICS) responses to morphine sulfate (MS), methionine enkephalin (ME) and leucine enkephalin (LE); (b) to determine the mechanism by which exogenous opiates mediate these responses; (c) to determine the type of receptor involved in mediating these responses and (d) to ascertain whether endogenous opiate-mediated responses may be vagally induced. The ICS responded to all three opiate agonists with tonic and phasic contractions, the latter being associated with increased spike activity. The ED(max) for ICS pressure response was 1 mug/kg for ME, 5 mug/kg for LE, and 150 mug/kg for MS. The distal ileum responded with increased spike activity and phasic contractions. The ED(max) for the ileal motility index response was 1.0 x 10(-1) mug/kg for ME, 1 mug/kg for LE, and 150 mug/kg for MS. Thus, both sites demonstrated similar dose-response relationships, both responding to at least 100 times lower doses of enkephalins than MS. The ICS contraction preceded ileal contractions. The ileal and ICS response was not antagonized by atropine, hexamethonium, phentolamine, propranolol, cinanserin, or tetrodotoxin. Naloxone, 600 mug/kg, antagonized the response to the enkephalins while 10 mug/kg antagonized the response to MS. Higher doses of the specific-receptor agonist SKF 10047 and kappa-receptor agonist ketocyclazocine were required before a contractile response was elicited. Electrical stimulation of the cervical vagus induced ICS contraction and a fall in blood pressure. The ICS contractile response but not the blood pressure response was inhibited by naloxone 1 mg/kg. These data indicate: (a) tonic and phasic ICS contraction followed by ileal contraction may be mediated through delta-type opiate receptors located in the muscle membrane and (b) opiate-mediated ICS contraction may be induced during vagal stimulation.

Animals↗
PubMed1982

Mechanism of deoxycholic acid stimulation of the rabbit colon.

Previous studies showed that deoxycholic acid (DCA) stimulated migrating action potential complexes (MAPC) in the colon. The aim of this study was to clarify the mechanism of DCA-stimulated colonic motility. Myoelectrical and contractile activity were measured in New Zealand White rabbits from a loop constructed in the proximal colon. During the control period, slow waves were present at a frequency of 10.8 +/- 0.5 cycle/min and there were 1.5 +/- 0.5 MAPC/ h. After adding DCA (16 mM) to the loop the slow wave activity was unchanged. However, MAPC increased to 15.1 +/- 2.4 MAPC/h (P less than 0.001). MAPC activity was not stimulated in the colonic smooth muscle outside the loop. The intraluminal addition of procaine or tetrodotoxin to the colonic loop inhibited the DCA-stimulated increase in MAPC activity (0.2 +/- 0.2 MAPC/h) (P less than 0.005). Intravenous administration of atropine or phentolamine also inhibited MAPC activity that had been stimulated by DCA (P less than 0.005). Pretreatment with 6-hydroxydopamine also inhibited an increase in MAPC activity. Propranolol, trimethaphan camsylate, or hexamethonium had no effect on DCA stimulation of MAPC activity. Although the concentration of bile salt increased in the mesenteric venous outflow from the colonic loop, the intravenous administration of bile salt did not stimulate colonic MAPC activity. These studies suggest: (a) the action of DCA on smooth muscle activity is a local phenomenon, (b) the increase in MAPC activity is dependent on intact cholinergic and alpha adrenergic neurons, and (c) an increase in the concentration of bile salts in the serum is not associated with an increase in colonic MAPC activity.

Action Potentials↗
PubMed1982

Metoclopramide to treat gastroparesis due to diabetes mellitus: a double-blind, controlled trial.

Ten patients with diabetic gastroparesis were selected for a randomized, double-blind, controlled trial of metoclopramide. Each patient had longstanding insulin-requiring diabetes mellitus and symptoms of gastric stasis. The patients were evaluated for the symptoms of gastric stasis and radionucleotide gastric emptying was measured before the patients entered the study and after they were given either metoclopramide or placebo treatment. Metoclopramide, 10 mg orally, stimulated an increase in the rate of gastric emptying (56.8% +/- 7.4%) in contrast to the response to placebo (37.6% +/- 7.7%) (p less than 0.01). The overall symptoms and symptoms of vomiting were markedly reduced during metoclopramide treatment in contrast to those during placebo treatment. Before the study five patients were constipated (less than three bowel movements per week); during metoclopramide treatment the patients' bowel habits were improved. There was a poor correlation between improved gastric emptying and decreased symptoms. Metoclopramide may improve symptoms of diabetic gastric stasis through two mechanisms: its peripheral effect on gastric smooth muscle, which increases gastric emptying; and its central effects on the chemoreceptor vomiting zone, which decrease nausea.

Adult↗