CGMP INHIBITS L-TYPE CA2-PHOSPHORYLATION IN RAT PINEALOCYTES( CHANNELCURRENTS THROUGH PROTEIN)

In this study, the effect of cGMP on the dihydropyridine-sensitive (L- type) Ca2+ current was investigated using the whole cell version of th e patch-clamp technique in rat pinealocytes. Dibutyryl-cGMP (1 x 10(-4 ) M) induced a pronounced inhibition of the L-type Ca2+ channel curren t, The dibutyryl-cGMP effect was concentration dependent, Elevation of cGMP by nitroprusside had a similar inhibitory action on the L-type C a2+ channel current, Norepinephrine, which increased cGMP in rat pinea locytes, also inhibited this current, The action of cGMP was independe nt of cAMP elevation since the cAMP antagonist, Rp-cAMPs, had no effec t on the inhibitory action of dibutyryl-cGMP. The involvement of cycli c GMP-dependent protein kinase was suggested by the blocking action of two protein kinase inhibitors, (1-(5-isoquinolinesulfonyl)-2-methylpi perazine (H7) and N(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA100 4), on the dibutyryl-cGMP effect on the L-type Ca2+ channel current, T aken together, these results suggest that (1) cGMP modulates L-type Ca 2+ channel currents in rat pinealocytes, causing inhibition of this cu rrent; (2) the action of cGMP appears to be independent of cAMP elevat ion; and (3) phosphorylation by cGMP-dependent protein kinase may be i nvolved.