Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, dispersed rat pancreatic acini exhibited secretin subsensitivity in their capacity to release amylase after preexposure to increasing concentrations of the muscarinic cholinergic agonist carbamylcholine. The present study also explores the potential mechanisms involved in this cellular desensitization phenomenon. Secretin subsensitivity of pancreatic acini pre-exposed to 10(-4) M carbamylcholine was observed only at secretin concentrations above 10(-8) M. The desensitized cells had not recovered 3 h after the cholinergic agonist exposure. In these acini, the adenylate cyclase pathway remained unaltered because cholera toxin, forskolin, and 8-Br-cAMP still induced weak, but normal, amylase release when compared with control acini. In vivo administration of pertussis toxin failed to protect the dispersed pancreatic acini against carbamylcholine-induced secretin subsensitivity. Moreover, cAMP production by these acini in response to secretin, cholera toxin, and forskolin was similar to that observed in control acini. Secretin stimulation of inositol phosphate (InsP1, InsP2, InsP3) production after carbamylcholine pre-exposure remained equivalent to that observed in acini that had never been exposed to the cholinergic agonist. Thus, after muscarinic cholinergic agonist exposure, pancreatic acini showed secretin subsensitivity in their capacity to release enzyme. This phenomenon appears to result from modifications at post-second messenger loci.
Pancreas 1989
PMID:Muscarinic cholinergic induced secretin subsensitivity in rat isolated pancreatic acini. Effects on amylase release, cyclic adenosine monophosphate and inositol phosphate formation. 247 85

Dispersed rat pancreatic acini were used to determine the effect of galanin on the exocrine pancreas and on basal and secretagogue-stimulated amylase secretion. Basal amylase secretion and amylase release stimulated by cholecystokinin octapeptide, bombesin, 12-o-tetradecanoyl-phorbol-13-acetate (TPA), secretin, and vasoactive intestinal peptide were not affected by galanin in doses ranging from 10(-12) to 10(-6) M. Galanin, however, significantly inhibited the amylase release stimulated by sub- and supramaximal doses of carbachol. A time course study showed that the inhibition by galanin occurred during the sustained phase of carbachol-stimulated amylase secretion. The inhibitory action of galanin disappeared in acini obtained from animals pretreated with pertussis toxin (PTX). These results suggest that galanin inhibits carbachol-stimulated amylase secretion through a mechanism related to a PTX-sensitive G protein.
Pancreas 1994 Mar
PMID:Effects of galanin on amylase secretion from dispersed rat pancreatic acini. 751 93

Constitutive membrane trafficking events are regulated by heterotrimeric G-proteins (G-proteins) in addition to their regulation by small GTP-binding proteins (smgs). Here, we used streptolysin O-permeabilized mouse pancreatic acini and compounds that interact with G-proteins, but not smgs, to examine whether G-proteins are also involved in regulated pancreatic exocytosis. The wasp venom mastoparan (10 microM) inhibited by 25-50% amylase release from permeabilized acini stimulated by various combinations of Ca2+, cyclic AMP (cAMP), 12-O-tetradecanoylphorbol 13-acetate, and guanosine (5'-[gamma-thio]triphosphate (GTP gamma S), while the inactive analogue Mas17 was without effect. Pretreatment of intact acini with pertussis toxin resulted in an approximately 30% reduction of amylase secretion from cells subsequently permeabilized and stimulated with calcium and GTP gamma S. Pretreatment of intact acini with cholera toxin increased stimulated amylase release by 30% from subsequently permeabilized cells, and this effect was mimicked by 8-Br-cAMP. The cAMP-dependent protein kinase inhibitor H-89 (3 microM) largely reversed the effect of cholera toxin, indicating that cholera toxin's effect is due to increased cellular cAMP levels. The inhibitory effects of mastoparan and pertussis toxin suggest that a Gi/Go-type G-protein(s) is (are) involved in the regulation of exocytosis. Since mastoparan inhibited exocytosis stimulated by all intracellular mediators tested, it indicates that the G-protein acts at a distal step in the exocytic process.
Pancreas 1995 May
PMID:Evidence of heterotrimeric G-protein involvement in regulated exocytosis from permeabilized pancreatic acini. 779 94

The purpose of this study was to characterize the nature and mechanisms of angiotensin II-evoked calcium signaling in AR42J cells. Cytosolic calcium concentrations were determined using fura-2-based microfluorimetry. Angiotensin II causes elevations in free cytosolic calcium ([Ca2+]i) in the rat pancreatic acinar cell line AR42J. The mechanisms of angiotensin II-evoked calcium signaling were examined using fura-2-based fluorescent digital microscopy. Angiotensin II caused dose-dependent increments in [Ca2+]i over a concentration range of 0.1-1,000 nM, with an average increment of 243 +/- 16 nM at an angiotensin II concentration of 1,000 nM. Dup753, an AT1-specific antagonist, inhibited angiotensin II-evoked signaling, whereas the AT2 antagonist PD123,319 had no effect. Preincubation with the phospholipase C inhibitor U73122 reduced the response in [Ca2+]i to 25% of that of the control. Thapsigargin abolished angiotensin II-evoked calcium signaling. The inositol 1,4,5-trisphosphate receptor antagonist heparin introduced by radiofrequency electroporation inhibited responses to 46 +/- 6% of controls. Angiotensin II-evoked signals were reduced in magnitude and duration by elimination of Ca2+ from the extracellular buffer. Preincubation with pertussis toxin (100 ng/ml) had no effect. Angiotensin II did not stimulate cyclic AMP or suppress vasoactive intestinal peptide stimulated cyclic AMP production over the concentration range that caused Ca2+ signaling.
Pancreas 1999 Mar
PMID:Calcium signaling induced by angiotensin II in the pancreatic acinar cell line AR42J. 1009 Apr 17

Islet amyloid polypeptide (IAPP) is produced in pancreatic beta cells. Intraislet function of IAPP is still uncertain. In the present study, we investigated effects of IAPP and somatostatin on stimulus-secretion coupling of beta cells in isolated rat pancreatic islets. Insulin secretion induced by 22.2 mM glucose was increased by an IAPP antiserum (0.1%) or an IAPP antagonist (IAPP8-37, 10 microM). Pretreatment of islets with pertussis toxin (PTX) abolished the stimulating effect of IAPP8-37 on glucose-induced insulin secretion. In contrast, IAPP antiserum and IAPP8-37 did not change insulin secretion induced by 30 mM KCl. Somatostatin (1 nM) inhibited insulin secretion induced by 22.2 mM glucose, 10 mM L-arginine, 25 microM forskolin, and 200 microM carbachol. IAPP (10 microM) enhanced the inhibitory effect of somatostatin on insulin secretion induced by L-arginine or forskolin. PTX pretreatment abolished the effects of somatostatin and IAPP on arginine-induced insulin secretion. In conclusion, IAPP regulates multiple steps in signal transductions of beta cells. The effects of IAPP on beta cells are mediated by PTX-sensitive regulatory G proteins.
Pancreas 2000 Apr
PMID:Islet amyloid polypeptide regulates multiple steps in stimulus-secretion coupling of beta cells in rat pancreatic islets. 1076 52

A human pancreatic cancer cell line, Capan-1, secretes the chemokines interleukin-8 (IL-8) and growth-related oncogene alpha (GROalpha). Capan-1 cells also express the chemokine receptor 2 (CXCR2), which is a Gialpha-protein coupled receptor. Growth of Capan-1 cells was inhibited when anti-IL-8 or anti-GROalpha monoclonal antibody was added into the culture medium. Pertussis toxin, which blocks Gialpha also demonstrated a growth-inhibitory effect on Capan-1 cells. These results indicated that IL-8 and GROalpha act on Capan-1 cells as growth factors in an autocrine manner through CXCR2.
Pancreas 2000 Jul
PMID:Autocrine growth effect of IL-8 and GROalpha on a human pancreatic cancer cell line, Capan-1. 1088 32