Inhibition of atrial natriuretic peptide secretion by forskolin in noncontracting cultured atrial myocytes.
Secretory rates for immunoreactive atrial natriuretic peptide (ANP) by 7 - 8 day-old primary cultures of atrial myocytes from adult rats (with myocyte contraction inhibited by tetrodotoxin (TTX)) were (a) constant for at least two hours, and (b) significantly slowed by forskolin (1, 5, and 25 microM), dibutyryl cyclic adenosine monophosphate (1 mM), or isobutylmethylxanthine (100 microM). The substantial rates of ANP secretion which persisted in cells rendered noncontracting either by inhibiting Ca2+ influx via reduction of external [Ca2+] to less than 10(-7) M or by inhibiting sarcoplasmic reticulum Ca2+ release with 100 microM ryanodine were significantly slowed by 25 microM forskolin, but forskolin sensitivity was lost by cells exposed simultaneously to external Ca2+ concentration of less than 10(-7) M and 100 microM ryanodine. Quiescent myocytes whose ANP secretory rate was depressed by forskolin remained responsive to secretory stimulation by phorbol ester.
Iida
H
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Department of Anatomy, Kyushu University, Fukuoka, Japan.
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000502:physiology; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D012636:Secretory Rate / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D012433:Ryanodine; D005576:Colforsin; C016276:8-bromocyclic GMP; D004533:Egtazic Acid; D003994:Bucladesine; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine