Biomedical subjects

T L Peeters

Publications and source records attributed to T L Peeters.

At least 73 records · Page 4Linked to original sources

PubMed1991

[The potentials of erythromycin derivatives in the treatment of gastrointestinal motility disorders].

In low dosages erythromycin imitates the effect of motilin on the gastrointestinal motility. In vitro experiments show that erythromycin is a motilin agonist: it displaces motilin which is bound to its receptor; it directly acts on smooth musculature and it possesses the same animal and tissue specificity. Structural changes cause adequate changes in the binding affinity and in the contractile activity. Several motilides such as erythromycin derivatives with prokinetic properties have no antibiotic activity, but they cause a distinct increase of the prokinetic activity. Motilides may be defined as a new group of prokinetic substances: the motilinomimetics. Erythromycin normalises the delayed evacuation of the stomach of solid and fluid food in diabetic, idiopathic and postvagotomy gastroparesis. For the treatment of gastrooesophageal reflux disease, gastritis, pathological overgrowth of the small intestine, hypokinesia of the gallbladder and the chronic obstipation erythromycin appears as a promising medicament. The substances with a stronger effect may become even still more useful medicaments. A better understanding of the relation between motilin and motilides may lead to new knowledge about the regulation of the gastrointestinal motility.

Biliary Tract↗

PubMed1990

Improvement of gastric emptying in diabetic gastroparesis by erythromycin. Preliminary studies.

Erythromycin mimics the effect of the gastrointestinal polypeptide motilin on gastrointestinal motility, probably by binding to motilin receptors and acting as a motilin agonist. Erythromycin may thus have clinical application in patients with disturbances of gastroduodenal motility, such as diabetic gastroparesis. To examine this possibility, we studied the effect of erythromycin on gastric emptying in 10 patients with insulin-dependent diabetes mellitus and gastroparesis. We studied the emptying of liquids and solids simultaneously on separate days after the intravenous administration of erythromycin (200 mg) or placebo, using a double-isotope technique and a double-blind, crossover design. Erythromycin shortened the prolonged gastric-emptying times for both liquids and solids to normal. For example, 120 minutes after the ingestion of a solid meal, mean (+/- SE) retention was 63 +/- 9 percent with placebo and 4 +/- 1 percent with erythromycin, as compared with 9 +/- 3 percent in 10 healthy subjects. The corresponding values 120 minutes after the ingestion of a liquid meal were 32 +/- 4, 9 +/- 3, and 4 +/- 1 percent, respectively. Gastric emptying also improved, but to a lesser degree, in the 10 patients after four weeks of treatment with oral erythromycin (250 mg three times a day). These preliminary results suggest that erythromycin may have therapeutic value in patients with severe diabetic gastroparesis.

Adult↗

PubMed1990

Dopamine interrupts gastrointestinal fed motility pattern in humans. Effect on motilin and somatostatin blood levels.

The aim of this study was to investigate the hypothesis that during the postprandial period in humans, dopamine interrupts the gastrointestinal motility pattern through a mechanism that is peptide-mediated. Fourteen normal human subjects were studied by means of intestinal manometry. After recording two consecutive migrating motor complexes a 900-kcal solid-liquid meal was given. In eight subjects 30 min after the meal, placebo or dopamine (5 micrograms/kg/min) was infused for 15 min and then the recording continued for 120 min. In the remaining six subjects dopamine was administered twice with a 90-min interval in between. In three subjects the first dopamine infusion after the meal was preceded by treatment with placebo, the second by domperidone (20 mg intravenous as bolus), in the other three subjects domperidone was given before the first dopamine infusion. Blood samples for the determination of somatostatin and motilin were drawn basally, during, and immediately after dopamine in seven subjects. The results show that dopamine interrupts the fed motility pattern, inhibiting the high antral waves, and activates a duodenal phase III of migrating motor complexes. The pretreatment with domperidone completely prevented the dopamine effect. Plasma levels of motilin increased significantly during dopamine, while somatostatin blood levels did not change. These findings support the hypothesis that a dopaminergic mechanism may modulate the cycling of duodenal motor complex in humans.

Adult↗

PubMed1990

Development of motilin receptors and of motilin- and erythromycin-induced contractility in rabbits.

The development of the motilin receptor was studied through contraction and binding studies of groups of three rabbits aged between 2 and 289 days. The contractility of small intestinal smooth muscle strips was measured isotonically. The aborally decreasing gradient in response to motilin, known to exist in adult rabbits, was already present at day 8 (maximum contractile responses expressed as a percent of the maximal response to acetylcholine were 77% +/- 9%, 34% +/- 10%, and 25% +/- 8% for duodenal, jejunal, and ileal strips, respectively). Throughout the observation period, the doses of motilin and its agonist erythromycin that were required to induce 50% of the response remained constant and were not significantly different from doses required for adults (their negative logarithms were 8.55 +/- 0.35 and 5.70 +/- 0.25, respectively). The correlation between the maximum contractile response toward motilin and erythromycin was almost perfect (r2 = 0.82). Binding studies with iodinated norleucine13-porcine motilin were performed using antral smooth muscle tissue homogenates. The maximum number of binding sites increased rapidly after 8 days (3.3 +/- 0.4 fmol/mg protein) and reached a peak at 21 days (20.7 +/- 1.4 fmol/mg protein), but decreased at that point toward the adult value (40 days, 10.6 +/- 1.3; 289 days, 9.8 +/- 1.1 fmol/mg protein). The dissociation constant, however, remained unchanged. The peak value of receptor density occurred at about the time that the rate of increase of the length of the intestine and of the weight of the antrum were at maximum levels (at 18 and 27 days, respectively). Motilin receptors are expressed early postnatally, and the regional gradient in sensitivity towards motilin is also established soon after birth. If applicable to humans, an early response to erythromycin may have therapeutic value.

Acetylcholine↗

PubMed1990

Gastrin, motilin and pancreatic polypeptide levels after two different parenteral regimens in infants.

We studied the effect of 2 different parenteral regimens upon gastrin, motilin and pancreatic polypeptide (PP) levels in infants. In 15 children, aged 1-25 months, plasma peptide levels were measured by radioimmunoassay in the fasting state and after a 2-h infusion of either a mixture of amino acids, glucose and lipids (A) or a mixture of amino acids and glucose (B) only. Wide interindividual fluctuations were noted, especially for motilin and PP, but, except for PP, intraindividual fluctuations were low. Indeed, a good correlation was found, not only between the 2 pre-infusion levels, but also between pre- and postinfusion levels in both experiments. In fact for all 3 peptides, pre- and postinfusion levels differed only slightly and non-significantly. We conclude that during parenteral feeding levels of motilin, PP and gastrin remain practically unchanged and are not influenced by the addition of lipids. In addition, during the observation period basal levels did not change, indicating that the mechanisms regulating basal secretion were not affected.

Amino Acids↗

PubMed1990

The effect of oral glucose, protein, fat and water loading on blood pressure and the gastrointestinal peptides VIP and somatostatin in hypertensive elderly subjects.

In elderly subjects blood pressure (BP) may fall after a meal. It can be reproduced by oral glucose, but the effect of fat and protein ingestion on postprandial BP has not been reported. Furthermore, we hypothesized that vasoactive gastrointestinal peptides are involved in this phenomenon. We studied 10 hypertensive elderly subjects (mean age 74 +/- 3 years) for the effects of oral glucose, fat, protein and water loading on BP in relation to plasma concentrations of vasoactive intestinal polypeptide (VIP), somatostatin and insulin. Glucose loading resulted in a decrease of mean arterial pressure by 14 +/- 2 mmHg (P less than or equal to 0.001). In contrast, the ingestion of fat, protein or water had no significant effect on BP. Somatostatin increased after fat and protein loading, whereas VIP increased only after fat loading. These data indicate that postprandial BP reduction in the elderly is related to glucose-related factors. The gut peptide VIP does not seem to play a role in this phenomenon.

Aged↗

PubMed1990

Effects of substance P on [Ca2+]i and force in intact guinea pig ileal smooth muscle.

In intact sheets of the guinea pig ileal longitudinal muscle, loaded with fura-2, both substance P (SP)- and K(+)-induced contractile responses are preceded by cytoplasmic free Ca2+ ([Ca2+]i) variations. In response to SP (10(-10)-10(-7) M), [Ca2+]i and force increased concentration dependently. From 10(-9) M on, the response was biphasic: an initial Ca2+ spike and force transient were followed by a tonic component. The [Ca2+]i and force vs. log [SP] curves were sigmoidal for the initial phasic component, while a homologous receptor desensitization caused a reduced tonic component of the [Ca2+]i and contractile response at higher concentrations of SP. Both intracellular Ca2+ release and Ca2+ influx play a role in the effect of the peptide. In depolarizing solutions (140 mM K+) and in Ca2(+)-free medium (2 mM EGTA), SP induced a transient increase in [Ca2+]i and force. The Ca2+ stores used by SP and acetylcholine (ACh) overlap. [Ca2+]i and force fell to base-line levels when the extracellular Ca2+ was reduced from 1.2 to 0.2 mM during stimulation with SP. Verapamil reduced the tonic response. We also studied the relation between [Ca2+]i and force for the peak and steady-state values after stimulation with increasing concentrations of SP and K+. The phasic force response was linearly related to log [Ca2+]i. During the sustained response to K+, the Ca2+ sensitivity of the contractile/regulatory proteins was decreased, whereas no changes were observed during prolonged stimulation with the peptide.

Animals↗

PubMed1990

[Interrelations between the presence or lack of bile and bile acids in the small-intestinal lumen, release of motilin and pancreatic polypeptide and migrating myoelectric complex in dogs].

5 male and 1 female dogs weighing 15-20 kg were used in the study. Animals underwent the functional cholecystectomy, bidirectional cannulation of the common bile duct and the implantation of 9 bipolar electrodes located in the stomach and small intestine. In 13 experiments performed on 4 dogs the interdigestive myoelectric activity was recorded and plasma motilin and PP levels were determined by radioimmunoassay during: 1) the control period where the spontaneous bile circulation was preserved, 2) bile depletion with or without intravenous motilin (56 pmol.kg-1.hr-1) infusion, 3) intraduodenal infusion of 50 mM Na-taurocholate with or without intravenous infusion of PP (400 pmol.kg-1.hr-1). During 88 additional experiments performed on all operated animals, which comprised the control studies, bile deprivation experiments and bile or bile acid infusions, the interdigestive myoelectric activity was recorded along with the estimation of sites of phase III origin. Motilin infusion at the lack of bile and bile acids in the intestine elicited the premature phase III in the duodenum, markedly increased the percentage of phases III originating from the stomach, inhibited the arrival of phase I of the myoelectric cycle and lowered plasma PP level. Infusion of PP despite the presence of bile acids in the small intestinal lumen caused the phase III originated from the proximal or mild jejunum and lowered plasma motilin level. Thus, unlike bile or bile acids, both motilin and PP are directly responsible for the appearance of phase III in the stomach and proximal small bowel of the dog. The luminal bile appears only to play a mediatory role influencing the release of the hormonal peptides examined here.

Animals↗

PubMed1990

[Inhibition of the interdigestive myoelectric cycles in dogs by a single administration of bile acids into the branch of the cranial mesenteric artery].

Experiments were performed on 10 fasted dogs equipped with perfused catheter which was placed into the branch of the cranial mesenteric artery supplying the short duodenal or jejunal segment. In addition, 9 bipolar electrodes for electromyographic examinations were implanted into the stomach and small bowel including the perfused intestinal segment. Na-taurocholate, Na-taurodeoxycholate (TD) and Na-taurochenodeoxycholate were infused for 2 hr in 2 different doses (reaching in blood, which supplies the intestine, the concentration about 7.5 and about 50 mumol.l-1) or injected for 0.5 min (reaching the concentration about 200 mumol.l-1 in the blood) close intraarterially to the animals. The lower dose of bile acid infused caused no significant changes in myoelectric activity. The higher dose of bile acid infused significantly inhibited the occurrence of action potentials (prolongation of phase I of the migrating myoelectric complex) for the period much longer than the bile acid infusion itself. Both stimulatory (the phase III-like myoelectric activity, vomiting) and inhibitory effects of action potentials as well as changes in frequency and amplitude of resting potentials were triggered by bile acid injection. Alterations induced by TD administration were the strongest. The immediate appearance of the inhibitory effect suggests the mediatory role of the nervous system in this response. In normal conditions the bile acids appear to regulate the motor function of the digestive tract solely when they enter the intestinal lumen. Their raised level in plasma, as observed in many liver and biliary tract diseases must give, as a consequence, an unfavourable effects which may be a cause for the arrival of gastrointestinal manifestations (the motor component) during a course of above affections.

Animals↗

PubMed1990

[Plasma motilin and diarrhea in ulcerative colitis].

Motilin basal level and that after carbohydrate load were radioimmunoassayed in 26 patients with ulcerative colitis. The results were correlated with the data on motor evacuatory activity of the gastrointestinal tract and clinical manifestations of diarrhea. Basal motilin level was found elevated as against the control (99 rg/ml) in all the patients and surpassed the norm (356-1001 rg/ml) in 6. A significant elevation of motilin content was associated with reduction of the amplitude and number of rhythmic type I contractions, as well as by increased number of type III (propulsive) waves and accelerated transport of the contents via the small intestine. No compensatory rarefying of acid discharge from the stomach, that was observed in reference subjects if transport of contents was accelerated, was detectable in the patients with ulcerative colitis. This resulted in acidification of the enteral medium (pH 5.6 +/- 0.6). Concomitant pancreatitis in 22 patients with reduced production of HCO3- and impaired cavitary hydrolysis of polymer substrate enhanced enteral medium acidification and changed its osmotic pressure. Specific features of enteral medium homeostasis disorders and of impairments of the gastrointestinal tract motor evacuatory function should be borne in mind when planning treatment strategy for diarrhea patients.

Adult↗

PubMed1989

The role of intracellular calcium stores in motilin induced contractions of the longitudinal muscle of the rabbit duodenum.

The contraction of longitudinal muscle strips of the rabbit duodenum in response to motilin and acetylcholine was investigated in normal and high K+-solutions in the presence and absence of external calcium, in order to demonstrate the existence of pharmaco-mechanical coupling for motilin and to examine whether the peptide mobilizes calcium from an intracellular store. In depolarized smooth muscle (140 mM K+), motilin (3.2 x 10(-9)-1 x 10(-7) M) and acetylcholine (1 x 10(-5) M) were still capable of causing a considerable, transient, concentration-dependent contraction in the presence of Ca2+. The 'extra'-contraction to motilin was not blocked by tetrodotoxin (1 microgram/ml) nor by atropine (10(-7) M), but acetylcholine (10(-5) M) was blocked by atropine. Verapamil (10(-7) M) could selectively block the K+ contraction without affecting the extra agonist contraction. Nitroprusside was ineffective up to 10(-4) M in high K+-solutions, but in normal Hepes-buffer it caused a concentration-dependent rightward shift of the concentration-response curve of motilin and acetylcholine contractions. In a calcium-depleted medium, high K+-depolarized muscle strips were still responsive to motilin and acetylcholine, but higher concentrations (10(-6) M) were needed than in the presence of calcium and the contractions reached only 57 +/- 11% and 74 +/- 9% respectively of the maximal contraction in 1.2 mM Ca2+ containing solutions. The response to motilin (10(-6) M) was not only smaller than that to acetylcholine (10(-5) M), it also faded more rapidly with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1989

Maternal and fetal endocrine pancreas in the spontaneously diabetic BB rat.

The maternal and fetal endocrine pancreas were investigated in the diabetic BB rat on day 21 of pregnancy. The maternal pancreas of the diabetic rat contained practically no insulin-positive B cells. The A and D cell mass were also decreased, while plasma glucagon and somatostatin levels were normal or increased, confirming previous data. Six of 11 diabetic rats had B-cell-specific surface antibodies (ICSA), whereas only 1 of 10 nondiabetic rats was ICSA-positive. The volume density of insulin-positive cells was decreased in the fetal pancreas of diabetic BB rats compared to fetuses of nondiabetic rats, but the volume density of glucagon- and somatostatin-positive cells remained normal. The B cells of these fetuses were ultrastructurally less granulated and showed signs of increased cellular activity. Plasma insulin levels were decreased while plasma glucagon and somatostatin concentrations were normal. ICSA were not detected in fetuses of nondiabetic and diabetic rats. There were no differences in the histology of the spleen and thymus between both groups of fetuses. Metabolic characterization of the growth-retarded fetuses of diabetic rats revealed, besides lower plasma insulin concentrations, increased branched chain amino acid levels, and normal plasma Sm/IGF-I levels. The main conclusions from this study are: (1) Severe maternal diabetes decreases the pancreatic insulin-positive cell mass and plasma insulin levels in the fetus, but not the A and D cell mass and function; (2) ICSA are not detectable in fetal plasma; (3) the influence of maternal BB rat diabetes on fetal endocrine pancreas and metabolic environment resembles that of severe streptozotocin-induced diabetes.

Animals↗

PubMed1989

Somatostatin analog octreotide (SMS 201-995) prevents the decrease in blood pressure after oral glucose loading in the elderly.

In elderly subjects blood pressure (BP) may fall after a meal. The mechanism of this phenomenon is unknown, but it has been suggested that it may be mediated by insulin and/or vasoactive gut hormones. We studied in normo- and hypertensive elderly subjects the effects of the synthetic long-acting somatostatin analog octreotide (SMS 201-995) on the BP reduction that follows oral glucose administration in subjects who are recumbent and on their postglucose plasma vasoactive intestinal polypeptide (VIP) and insulin concentrations. After placebo treatment, mean arterial pressure fell by 15 +/- 1 mm Hg (P less than 0.001) in the 10 hypertensive subjects and by 7 +/- 2 mm Hg (P less than 0.01) in the 10 normotensive subjects. In contrast, when 50 micrograms octreotide were given sc, BP did not change significantly in either group. Oral glucose did not induce a rise in plasma VIP after either octreotide or placebo administration. The postglucose rises in plasma glucose concentrations were similar after octreotide and placebo treatments in both groups. After placebo administration the postglucose plasma insulin levels increased from 79 to 519 pmol/L in the hypertensive subjects and from 63 to 464 pmol/L in the normotensive subjects, whereas after octreotide treatment plasma insulin increased little in either group. These data indicate that treatment with octreotide holds promise for patients with symptomatic postprandial hypotension, and that VIP does not seem to play a role in this phenomenon.

Administration, Oral↗

PubMed1989

[Bile fractions and bile secretory component of the migrating myoelectric complex in dogs].

In 4 dogs the functional cholecystectomy was performed, then the common bile duct was cannulated and 9 bipolar electrodes were implanted into the stomach and small intestine. During the interdigestive period when the experiments were carried out both bile flow and electric activity of the gastrointestinal tract were monitored under the following conditions: 1) short or long bile depletion periods, 2) intraduodenal infusions of 50 mM sodium taurocholate, sodium taurodeoxycholate or sodium taurochenodeoxycholate, 3) intraduodenal bile infusions. Total bile acid content was determined in bile samples, then both bile acid-dependent (BAF) and bile acid-independent fractions (BAIF) of bile were calculated. The appearance of the bile secretory component was in 65% correlated with phase III of the MMC while the height of its amplitude usually exceeded 100% of the initial value. In all experimental groups the marked increase in BAIF was followed by a slight enhancement of BAF or its absence. Fluctuations of the biliary fractions were determined by a degree of depletion of the systemic bile acid pool. The changes described were more distinct during infusions of dihydroxy bile acids. The results suggest the importance of BAIF in the appearance of the bile secretory component of the MMC.

Action Potentials↗

PubMed1989

[Bile acids and electric activity of the stomach and small intestine in dogs during the interdigestive period].

Examinations were carried out on 4 fasted dogs using chronic experimental model. In the animals the functional cholecystectomy was performed, 2 cannulas were inserted into the common bile duct and 9 pairs of electrodes were ++implanted from pyloric antrum till ileum. After the disconnection of the exteriorized tubes enterohepatic circulation of bile acid was interrupted. Then, sodium salts of taurocholic, taurodeoxycholic and taurochenodeoxycholic acids (at the concentrations 5, 20 and 50 mM) alone and in the combination were infused intraduodenally and myoelectric activity was continuously recorded. During control experiments the enterohepatic circulation was preserved. Application of individual bile acids at higher concentrations and their combinations caused significant (about 60 min) prolongation of cycle intervals changing fundamentally duration of both phases I and II along with the alteration of their relative proportion. In the control group duration, of both phase I and II as measured in mid jejunum lasted 47 +/- 3 and 38 +/- 2 min, respectively (ratio 1.24). During administration of 50 mM Na-taurodeoxycholate these values were respectively equal to 6 +/- 2 (P less than 0.01) and 122 +/- 31 min (P less than 0.05), respectively, and the ratio was 0.05. Infusions of primary bile acids resulted in the greater percentage of phases III which originated from the stomach. Propagation velocity of phase III as measured in the jejunum was about 50-100% faster, mainly during the infusion of dihydroxy bile acids. The results have suggested that bile acids are responsible for majority of alterations of the myoelectric cycle induced by intraduodenal bile administration. These changes could be interpreted as the disappearing tendency of the cycle but their mechanisms still remain to be elucidated.

Action Potentials↗

PubMed1989

[Electrophysiological changes related to the exclusion of bile from the small intestine of dogs during the interdigestive period].

The effect of interruption of enterohepatic circulation of bile acids on the interdigestive electrical activity of gastrointestinal tract was studied on 6 dogs. Animals underwent the functional cholecystectomy and cannulation of common bile duct. 9 bipolar electrodes were then implanted into the stomach and small intestine. Electrical activity was recorded during 2-3 and 4-10 hr periods of bile diversion with and without intravenous infusion of sodium taurocholate and also during intraduodenal bile acid infusions. In control group the enterohepatic circulation of bile acids was maintained. During longer bile diversion intervals of the myoelectric cycle increased from 104 +/- 7 min in control group till 133 +/- 8 min (P less than 0.05) mainly due to the prolongation of phase II. During the latter period a specific pattern of spike bursts (bile diversion myoelectric pattern, BDMP) was observed. This phenomenon was induced by the lack or deficiency in bile acids in the intestinal lumen (the bile acid depletion pattern, BADP) and it was inhibited during bile acid administration. When the biliary drainage was continued, 82% of an activity fronts originated in the jejunum. Their propagation velocities in upper jejunum were 9 +/- 1 cm.min-1 as compared to the control value, 6 +/- 0.05 cm.min-1 (P less than 0.05). These changes were approximate to those observed during intravenous taurocholate infusion. However, the cycle duration lasting 90 +/- 9 min was not significantly altered and BADP was less frequently recorded. The results obtained confirm the significant role of bile and bile diversion in modification of the myoelectric activity of stomach and small bowel in dogs.

Action Potentials↗

PubMed1989

[Bile secretion and motilin and pancreatic polypeptide (PP) release in dogs during infusion of bile acids in the interdigestive period].

In 4 dogs functional cholecystectomy was performed, 2 cannulas were inserted into the common bile duct and 9 pairs of the electrodes were implanted in the stomach and small intestine. During chronic experiments exteriorized tubes were disconnected for both monitoring of biliary secretion and intraduodenal infusions of buffer, standard bile, Na-taurocholate, Na-taurodeoxycholate and Na-taurochenodeoxycholate used in 3 various concentrations as well as mixtures of these salts. During other experiments Na-taurocholate was infused intravenously. In the control group biliary tubes were not opened. The interdigestive myoelectric activity was recorded simultaneously and blood samples were taken for motilin and PP radioimmunoassays. Biliary secretion and motilin release were the highest during phase III of the myoelectric cycle. During both bile acid depletion and intravenous infusion no clear fluctuation of biliary secretion was observed. Bile and bile acid infusions resulted in the increased motilin release about 20-50% depending on bile acid concentration and in more than 50% inhibition of PP release. Plasma level of PP fluctuated in relation to the phase of the cycle entirely during bile acid depletion. The results suggest that the regulation of myoelectric cycle by bile acid secretion can be mediated by motilin and PP as well as confirm the important role of small intestine in the modification of PP release.

Animals↗

PubMed1988

Effect of different calcium modulators on motilin-induced contractions of the rabbit duodenum. Comparison with acetylcholine.

Motilin and acetylcholine (ACh) have a direct contractile effect on rabbit small intestinal smooth muscle. To explore the role of calcium influx in these contractions, we studied the effect of extracellular calcium concentration and of calcium antagonists on the response of longitudinal muscle preparations from rabbit duodenum. Motilin- (10(-7) M) and ACh- (10(-4) M)-induced contractions were abolished in Ca2+-depleted medium. ACh (10(-4) M) or motilin (10(-8) and 10(-7) M) increased the contractile response to added Ca2+ to 130 +/- 6%, 129 +/- 10% and 145 +/- 5% of the maximal response to Ca2+ added alone (10 mM in a cumulative concentration response curve). The sensitivity to Ca2+ was greater in the presence of ACh and motilin (EC50 = 1.0 and 1.1 mM Ca2+) than in the absence of any agonist (1.7 mM). In cumulative concentration response (CCR) curves for motilin and ACh, pD2'-values were 7.0 and 6.6 for diltiazem, 8.4 and 7.8 for verapamil (two calcium entry blockers), 5.6 and 5.2 for TMB-8 (an inhibitor of intracellular calcium), 5.3 and 5.2 for TFP (a calmodulin-antagonist). All CCR-curves showed metactoid-like action of the antagonistic drugs. We conclude that ACh and motilin cause calcium to enter the smooth muscle cell. They are probably operating via separate channels, and use a mechanism which differs from K+-induced influx. Intracellular calcium stores appear to play a minor role in these contractions.

Acetylcholine↗