Enhancers of cytosolic cAMP augment depolarization-induced exocytosis from pancreatic B-cells: evidence for effects distal to Ca2+ entry.
We have investigated the effects of cAMP-enhancing agents on depolarization-induced membrane capacitance increases (delta Cm) in single rat pancreatic B-cells. Concentrations of IBMX, 8-CPT cAMP and forskolin, which enhance cAMP and insulin release, all enhance depolarization-induced delta Cm's seen in response to single voltage-clamp pulses and reduce the depression of delta Cm responses often seen with trains of pulses. These effects often occur in the absence of changes in peak Ca2+ current or the total Ca2+ charge entry during the depolarizing pulse. These data suggest that cAMP-modulating maneuvers may directly affect the mechanism of insulin granule mobilization into a readily releasible store or fusion at a discharge site.
Gillis
K D
KD
Department of Medicine (Jewish Hospital), Washington University Medical Center, St. Louis, Mo. 63110.
Misler
S
S
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D005089:Exocytosis / Q000187:drug effects*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013873:Thionucleotides / Q000494:pharmacology
D015220:Calcium Channels; D007328:Insulin; D013873:Thionucleotides; D005576:Colforsin; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine