A calmodulin antagonist (W-7) and a protein kinase C inhibitor (H-7) have no effect on atrial natriuretic peptide release induced by atrial stretch.
The role of intracellular signals in the regulation of atrial natriuretic peptide (ANP) release was investigated using isolated rat left atria. Dibutyryl cyclic AMP and dibutyryl cyclic GMP had no effect on ANP release. Arginine vasopressin and phenylephrine, both of which activate the polyphosphoinositide system and consequently both the diacylglycerol-protein kinase C system and the Ca2+-Ca2+ receptor system, stimulated ANP release dose-dependently. The ANP release stimulated by phenylephrine was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist, and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), a protein kinase C inhibitor. Atrial stretch stimulated ANP release, but the release was not inhibited by W-7 or H-7. These results suggest that the mechanism responsible for phenylephrine-induced ANP release differs from that for stretch-induced ANP release.
Ishida
A
A
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Tanahashi
T
T
Okumura
K
K
Hashimoto
H
H
Ito
T
T
Ogawa
K
K
Satake
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D016275:Atrial Function; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D010812:Physical Stimulation; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology*
D002147:Calmodulin; D007546:Isoquinolines; D010879:Piperazines; D013449:Sulfonamides; D001127:Arginine Vasopressin; D010656:Phenylephrine; D003995:Dibutyryl Cyclic GMP; D003994:Bucladesine; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C