Two distinct effects of cGMP on cytosolic Ca2+ concentration of rat pancreatic beta-cells.
The present study investigated the effects of cGMP on cytosolic Ca(2+) concentration ([Ca(2+)](c)) of isolated rat pancreatic beta-cells. In the presence of 7.0 mM glucose, NOC 7, a nitric oxide (NO) donor, caused an increase in [Ca(2+)](c) of the beta-cells, which was abolished by the soluble guanylate cyclase inhibitor ODQ. Similar [Ca(2+)](c) elevation was evoked by 8-bromo-cGMP. The [Ca(2+)](c) elevating responses to NOC 7 and 8-bromo-cGMP were abolished by nicardipine or in a Ca(2+)-free medium, but were not affected by thapsigargin, suggesting that they are produced by the Ca(2+) influx through L-type voltage-operated Ca(2+) channels. In contrast, NOC 7 and 8-bromo-cGMP decreased the [Ca(2+)](c) when it was raised in advance by the elevation of external K(+) concentration to 30 mM or by 4-aminopyridine. The pretreatment with thapsigargin almost abolished the [Ca(2+)](c) reduction induced by the agents, suggesting that the action is likely to be primarily attributable to an acceleration of the Ca(2+) sequestration into the endoplasmic reticulum. These results suggest that cGMP has two distinct effects on the [Ca(2+)](c) of rat pancreatic beta-cells: a facilitation of the Ca(2+) influx through L-type voltage-operated Ca(2+) channels and an acceleration of the Ca(2+) sequestration in the endoplasmic reticulum.
Ishikawa
Tomohisa
T
Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. ishikat@u-shizuoka-ken.ac.jp
Kaneko
Yukiko
Y
Sugino
Fumi
F
Nakayama
Koichi
K
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D014044:Tolbutamide / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; C115239:3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine; D004791:Enzyme Inhibitors; D006834:Hydrazines; D007004:Hypoglycemic Agents; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D011810:Quinoxalines; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D014044:Tolbutamide; D015761:4-Aminopyridine; D006152:Cyclic GMP; D005947:Glucose; D011188:Potassium; D002118:Calcium; D004121:Dimethyl Sulfoxide