Effect of atriopeptin II on Ca influx, contractile behavior and cyclic nucleotide content of cultured neonatal rat myocardial cells.
The present study was carried out to evaluate the effects of biologically active atriopeptin II (APII) in synchronously contracting monolayer cultures of rat ventricular myocytes. The effects of 10 nM APII on Ca influx, contractile behavior and cyclic nucleotide content of the cells were measured. Applied acutely APII had no effect on Ca influx. There was however a time-dependent effect such that after 30 min Ca influx (pmol/cm2/s) had declined from a control (mean +/- S.E.M.) of 1.53 +/- 0.16 to 1.02 +/- 0.07 (P less than 0.001; n = 6). There was parallel decline in both the magnitude and velocity of cell edge motion which was maximal in 30 min at which time cell edge motion measured 65.3 +/- 4.4% of control. Treatment with APII for 30 min decreased cAMP (pmol/mg protein) from 5.35 +/- 0.17 to 2.86 +/- 0.24 (P less than 0.001; n = 5). At the same time cGMP (pmol/mg protein) increased from 0.86 +/- 0.21 to 2.14 +/- 0.33 (P less than 0.001; n = 5). Further studies elucidated the fact that the decline in Ca influx and contractile behavior was dependent on the decrease in cAMP rather than the increase in cGMP. Pre-treatment of the cells with 5 ng/ml of pertussis toxin to ADP-ribosylate the Gi protein abolished the effects of APII on cAMP, Ca influx and contractile behavior. The results indicate that in myocardial cells, as in other cells, APII stimulates guanylate cyclase and inhibits adenylate cyclase. The resultant fall in cAMP decreases Ca influx and negatively influences the contractile behavior of the cells.
McCall
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Department of Medicine, University of Texas Health Science Center, San Antonio 78284.
Fried
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D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D051381:Rats
D000067956:Adenylyl Cyclase Inhibitors; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium