title: In rat pinealocytes the cyclic GMP response to NO is regulated by Ca2+ and protein kinase C.
abstract: There is ample evidence that beta-adrenergic stimulation of cyclic GMP formation is potentiated by alpha1-adrenergic mechanisms, the latter leading to elevation of intracellular Ca2+ concentration ([Ca2+]i) and protein kinase C (PKC) activation. Recent studies have shown that nitric oxide synthase (NOS) and nitric oxide (NO) are a component of the adrenoceptor-cyclic GMP signalling pathway. The aim of the present investigation was to study the roles of alpha1-adrenergic mechanisms, Ca2+ and PKC on NO-stimulated cyclic GMP formation. To this end suspension cultures of rat pinealocytes were treated with the NO donor sodium nitroprusside (SNP) in the presence of alpha1-adrenergic agonists, [Ca2+]i-elevating substances, PKC inhibitors, followed by measurement of cyclic GMP accumulation. It was found that alpha1-adrenergic stimulation did not affect NO-activated cyclic GMP synthesis. Therefore alpha1-mechanisms act prior to NO induction of cyclic GMP. Agents, which elevate [Ca2+]i depressed NO-induced cyclic GMP formation. Since literature data show that Ca2+ stimulates pineal NO formation it is apparent that Ca2+ has antagonistic effects in the pineal adrenoceptor-cyclic GMP signalling pathway. The inhibitory effect of Ca2+ was unchanged after inhibition of phosphodiesterases suggesting that it may interfere with cytosolic guanylyl cyclase activation. Inhibition of PKC, but not of other protein kinases, decreased NO-activated cyclic GMP formation. Therefore it appears that non-alpha1-adrenergic-regulated PKC possesses a regulatory rote in NO-induced cyclic GMP formation.
authors.affiliation: Department of Anatomy, Johannes Gutenberg University, Mainz, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Spessert
authors.forename: G
authors.initials: G
authors.lastname: Hill
authors.forename: L
authors.initials: L
authors.lastname: Vollrath
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D010870:Pineal Gland / Q000166:cytology / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002147:Calmodulin; D010726:Phosphodiesterase Inhibitors; D047428:Protein Kinase Inhibitors; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D010042:Ouabain; D011493:Protein Kinase C; D010744:Phosphoric Monoester Hydrolases; D006152:Cyclic GMP; D007545:Isoproterenol; D002118:Calcium