ABSTRACT
In dispersed acini prepared from guinea pig pancreas, removing extracellular calcium did not alter the basal rate of amylase release but reduced the stimulation of enzyme release caused by cholecystokinin, carbachol, secretin, and vasoactive intestinal peptide as well as that caused by derivatives of cyclic nucleotides. In acini incubated in a calcium-free, EGTA-containing medium the increase in amylase release caused by each secretagogue tested did not change during the initial 10 min of incubation, decreased by approximately 65% during the subsequent 40 min, and remained constant thereafter. Removing extracellular calcium did not alter the maximally effective concentrations of cholecystokinin or vasoactive intestinal peptide but abolished the decrease in stimulated enzyme secretion seen with supramaximal concentrations of cholecystokinin. Incubating pancreatic acini with cholecystokinin or carbachol plus secretin or vasoactive intestinal peptide caused potentiation of amylase release, and removing extracellular calcium reduced the stimulation of enzyme release caused by the two secretagogues in combination but did not alter their potentiating interactions.
Subject(s)
Amylases/metabolism , Calcium/pharmacology , Pancreas/metabolism , Animals , Carbachol/antagonists & inhibitors , Cholecystokinin/antagonists & inhibitors , Dose-Response Relationship, Drug , Guinea Pigs , In Vitro Techniques , Secretin/antagonists & inhibitors , Vasoactive Intestinal Peptide/antagonists & inhibitorsABSTRACT
In dispersed acini prepared from guinea pig pancreas, ethanol inhibited the increase in amylase secretion caused by cholecystokinin, carbachol, secretin, or vasoactive intestinal peptide. Ethanol did not alter binding of [125I] vasoactive intestinal peptide to pancreatic acinar cells or the inhibition of binding cause by secretin or vasoactive intestinal peptide. Ethanol potentiated the increase in adenylate cyclase activity and cellular adenosine 3':5'-monophosphate caused by secretin or vasoactive intestinal peptide. This potentiating action was reversible and could also be detected with straight-chain alcohols having fewer than seven carbon atoms. At sufficiently high concentrations, straight-chain alcohols having more than two carbon atoms inhibited the action of secretin or vasoactive intestinal peptide on adenylate cyclase activity, and this and this action was irreversible.
Subject(s)
Ethanol/pharmacology , Gastrointestinal Hormones/pharmacology , Pancreas/metabolism , Secretin/pharmacology , Vasoactive Intestinal Peptide/pharmacology , 1-Propanol/pharmacology , Adenylyl Cyclases/metabolism , Alcohols/pharmacology , Amylases/metabolism , Animals , Carbachol/pharmacology , Cholecystokinin/pharmacology , Cyclic AMP/metabolism , Guanylyl Imidodiphosphate/pharmacology , Guinea Pigs , In Vitro Techniques , Male , Methanol/pharmacology , Octanols/pharmacology , Pancreas/enzymology , Vasoactive Intestinal Peptide/metabolismABSTRACT
In dispersed acini prepared from guinea pig pancreas, peptides isolated from amphibian skin (caerulein, bombesin, litorin, and physalaemin) as well as eledoisin, a peptide isolated from the posterior salivary gland of a Mediterranean octopod, caused a significant increase in amylase release. Each amphibian peptide potentiated the stimulation of amylase release caused by vasoactive intestinal peptide or secretin in that the increase in amylase release caused by an amphibian peptide plus vasoactive intestinal peptide or secretin was significantly greater than the sum of the increase caused by each secretagogue acting alone. Potentiation of amylase secretion did not occur with an amphibian peptide plus cholecystokinin or carbachol.
Subject(s)
Amylases/metabolism , Pancreas/metabolism , Peptides/pharmacology , Amphibians/metabolism , Animals , Bombesin/pharmacology , Carbachol/pharmacology , Ceruletide/pharmacology , Cholecystokinin/pharmacology , Drug Therapy, Combination , Eledoisin/pharmacology , Guinea Pigs , In Vitro Techniques , Male , Physalaemin/pharmacology , Skin/metabolismABSTRACT
We have described two patients with propranolol-induced severe diarrhea, confirmed by rechallenge with the drug. In both cases the diarrhea was readily reversible with discontinuation of the drug.
Subject(s)
Diarrhea/chemically induced , Propranolol/adverse effects , Atrial Flutter/drug therapy , Female , Humans , Hypertension/drug therapy , Male , Middle Aged , Propranolol/therapeutic use , Tachycardia/drug therapyABSTRACT
In homocystinuria due to cystathionine synthase deficiency thromboembolism is a major cause of mortality and morbidity. Recent studies by others identified an abnormally shortened platelet survival and increased platelet vacuolization in patients with homocystinuria. When we studied six additional patients, however, we found the platelet survival to be within normal limits for each. The mean survival (+/-1 S.D.) was 9.75+/-0.94 days (normal, 9.27+/-1.06). In addition, platelets from five patients with homocystinuria and three obligate heterozygotes could not be distinguished from those of seven normal control subjects by electron microscopy. Specifically, no increased vacuolization was observed. Genetic heterogeneity, technical differences of differences in plasma homocystine concentrations could account for these descrepant results. The mechanism of thrombosis in homocystinuria remains an open question.
