Stimulation of cyclic ADP-ribose synthesis by acetylcholine and its role in catecholamine release in bovine adrenal chromaffin cells.
Cyclic ADP-ribose (cADPR) is suggested to be a novel messenger of ryanodine receptors in various cellular systems. However, the regulation of its synthesis in response to cell stimulation and its functional roles are still unclear. We examined the physiological relevance of cADPR to the messenger role in stimulation-secretion coupling in cultured bovine adrenal chromaffin cells. Sensitization of Ca2+-induced Ca2+ release (CICR) and stimulation of catecholamine release by cADPR in permeabilized cells were demonstrated along with the contribution of CICR to intracellular Ca2+ dynamics and secretory response during stimulation of intact chromaffin cells. ADP-ribosyl cyclase was activated in the membrane preparation from chromaffin cells stimulated with acetylcholine (ACh), excess KCl depolarization, and 8-bromo-cyclic-AMP. ACh-induced activation of ADP-ribosyl cyclase was dependent on the influx of Ca2+ into cells and on the activation of cyclic AMP-dependent protein kinase. These and previous findings that ACh activates adenylate cyclase by Ca2+ influx in chromaffin cells suggested that ACh induces activation of ADP-ribosyl cyclase through Ca2+ influx and cyclic AMP-mediated pathways. These results provide evidence that the synthesis of cADPR is regulated by cell stimulation, and the cADPR/CICR pathway forms a significant signal transduction for secretion.
Morita
K
K
Department of Pharmacology, Hiroshima University School of Dentistry, 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan.
Kitayama
S
S
Dohi
T
T
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000109:Acetylcholine / Q000494:pharmacology*; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000096:biosynthesis; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism*; D036563:Cyclic ADP-Ribose; D004110:Diltiazem / Q000494:pharmacology; D004789:Enzyme Activation; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D012604:Scorpion Venoms / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D002121:Calcium Channel Blockers; D002395:Catecholamines; D012604:Scorpion Venoms; C105848:imperatoxin I; D036563:Cyclic ADP-Ribose; D012433:Ryanodine; D000246:Adenosine Diphosphate Ribose; D002110:Caffeine; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D004110:Diltiazem; D000109:Acetylcholine; D002118:Calcium