Cyclic GMP potentiates phenylephrine but not cyclic ADP-ribose-evoked calcium release from rat lacrimal acinar cells.
In the present study, we describe a role for cyclic GMP (cGMP) in the signalling pathway that leads from alpha-adrenergic receptor activation to intracellular Ca2+ mobilization in rat lacrimal acinar cells. The alpha-adrenergic agonist, phenylephrine, stimulates intracellular Ca2+ release which is blocked by inhibitors of guanylate cyclase and cGMP-dependent protein kinase Ia. The membrane-permeable cGMP analogues, dibutyryl-cGMP and 8-bromo-cGMP, potentiate ( approximately 5-fold) the Ca2+ response to submaximal phenylephrine stimulation. In contrast, the same cGMP analogues have no effect on cyclic ADP-ribose-evoked Ca2+ release from permeabilized lacrimal acinar cells. Collectively, these findings suggest that cGMP, via cGMP-dependent protein kinase I alpha , is required for intracellular Ca2+ release following alpha-adrenergic receptor activation in lacrimal acinar cells.
Jorgensen
T D
TD
Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark.
Dissing
S
S
Gromada
J
J
D000109:Acetylcholine / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D036563:Cyclic ADP-Ribose; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007700:Kinetics; D007765:Lacrimal Apparatus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D036563:Cyclic ADP-Ribose; D010656:Phenylephrine; D000246:Adenosine Diphosphate Ribose; D019335:Nitroarginine; C016276:8-bromocyclic GMP; D003995:Dibutyryl Cyclic GMP; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D000109:Acetylcholine; D002118:Calcium