cGMP inhibits L-type Ca2+ channel currents through protein phosphorylation in rat pinealocytes.
In this study, the effect of cGMP on the dihydropyridine-sensitive (L-type) Ca2+ current was investigated using the whole cell version of the patch-clamp technique in rat pinealocytes. Dibutyryl-cGMP (1 x 10(-4) M) induced a pronounced inhibition of the L-type Ca2+ channel current. The dibutyryl-cGMP effect was concentration dependent. Elevation of cGMP by nitroprusside had a similar inhibitory action on the L-type Ca2+ channel current. Norepinephrine, which increased cGMP in rat pinealocytes, also inhibited this current. The action of cGMP was independent of cAMP elevation since the cAMP antagonist, Rp-cAMPs, had no effect on the inhibitory action of dibutyryl-cGMP. The involvement of cyclic GMP-dependent protein kinase was suggested by the blocking action of two protein kinase inhibitors, (1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) and N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), on the dibutyryl-cGMP effect on the L-type Ca2+ channel current. Taken together, these results suggest that (1) cGMP modulates L-type Ca2+ channel currents in rat pinealocytes, causing inhibition of this current; (2) the action of cGMP appears to be independent of cAMP elevation; and (3) phosphorylation by cGMP-dependent protein kinase may be involved.
Chik
C L
CL
Department of Medicine, University of Alberta, Edmonton, Canada.
Liu
Q Y
QY
Li
B
B
Karpinski
E
E
Ho
A K
AK
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D010870:Pineal Gland / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides; D013873:Thionucleotides / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D013873:Thionucleotides; D009599:Nitroprusside; C016957:adenosine-3',5'-cyclic phosphorothioate; D003995:Dibutyryl Cyclic GMP; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D000242:Cyclic AMP; D006152:Cyclic GMP; D009543:Nifedipine; D009638:Norepinephrine