The responsiveness of the endogenous inhibitor of cAMP-dependent protein kinase to isoproterenol after prolonged treatment with nifedipine.
In the present study the response of the type I inhibitor activity to isoproterenol was used as an indirect index both of cAMP generation and beta-adrenergic receptor reactivity. Our results suggest that nifedipine, after prolonged treatment, produces subsensitivity in beta-adrenergic transmission without changes in the basal level of cAMP. Administration of isoproterenol produced a dose-dependent decrease of the type I inhibitor activity (an endogenous inhibitor of cAMP-dependent protein kinase, Walsh inhibitor) in the frontal cortex and hippocampus of rats. Prolonged treatment with nifedipine (5 mg kg-1 i.p., twice daily, 21 days) did not change the basal activity of the type I inhibitor, but markedly reduced the response of the type I inhibitor activity to isoproterenol. In the treated animals a significant decrease of the type I inhibitor was seen when isoproterenol was used in much higher doses than in control rats.
Zalewska-Kaszubska
J
J
Department of Pharmacodynamics, Medical University, Lodz, Poland.
Marczak
G
G
Wejman
I
I
Wiktorowska
A
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D010455:Peptides / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013268:Stimulation, Chemical
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011943:Receptors, Adrenergic, beta; C085074:Walsh peptide; D011433:Propranolol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D009543:Nifedipine; D007545:Isoproterenol