Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In dispersed acini from rat pancreas, verapamil (a phenylalkylamine calcium channel blocker) potentiated amylase secretion stimulated by vasoactive intestinal peptide (VIP), secretin, peptide histidine isoleucine, helodermin, forskolin, and 8-bromocyclic AMP. The action of verapamil on VIP-stimulated amylase secretion was detectable at 10 microM verapamil and maximal at 100 microM verapamil. Verapamil did not alter binding of 125I-VIP, basal cAMP, the increase in cAMP caused by VIP, or the increase in cAMP-dependent protein kinase caused by VIP. The effects of verapamil on stimulated amylase secretion were fully reversible and could be reproduced by nicardipine (a 1,4-dihydropyridine calcium channel blocker) and diltiazem (a benzothiazepine calcium channel blocker), but not by cinnarizine (a piperazine calcium channel blocker). Although 300 microM verapamil increased outflux of 45Ca, 100 microM verapamil, the concentration that produced maximal potentiation of VIP-stimulated amylase secretion, did not alter 45Ca outflux. Our results indicate that the action of verapamil to potentiate amylase secretion stimulated by secretagogues that activate the cAMP pathway occurs at a step that is distal to the activation of cAMP-dependent protein kinase.
Pancreas 1993 Mar
PMID:Effect of verapamil on the cyclic AMP-mediated pathway for amylase secretion in rat pancreatic acini. 768 80

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