Differential effects of somatostatin on atrial and ventricular contractile responses in guinea pig heart: influence of pretreatment with islet-activating protein.
The effects of somatostatin on the contractile response of guinea pig cardiac preparations were investigated and compared with those of carbachol and adenosine. Somatostatin produced a concentration-dependent negative inotropic effect in the left atria, which was accompanied by a decrease in action potential duration. The maximum decrease in contractility which was obtained at 3 x 10(-6) M was around 40% of the predrug control values and far less than those produced by carbachol and adenosine. Somatostatin failed to produce inotropic effect on the papillary muscle and did not influence the spontaneously beating rate of the right atria. In the papillary muscles, however, somatostatin inhibited the positive inotropic effect of isoproterenol in a concentration-dependent manner as did carbachol and adenosine. In addition, somatostatin caused a significant inhibition of the isoproterenol-induced increase in cyclic AMP levels without affecting the basal level of cyclic AMP. In the papillary muscle, the inhibitory effect of somatostatin on the positive inotropic response to isoproterenol was significantly attenuated by pretreatment with islet-activating protein, and was significantly antagonized by the somatostatin antagonist cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)]. These results suggest that somatostatin receptors in guinea pig ventricular muscles are coupled with adenylate cyclase via islet-activating protein-sensitive GTP-binding protein, whereas the negative inotropic effect of somatostatin in the left atria might be mediated by a subtype of somatostatin receptors which is different from that in the ventricle.
Endou
M
M
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Hattori
Y
Y
Nakaya
H
H
Kanno
M
M
D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D037342:Pertussis Toxin; D013004:Somatostatin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D010566:Virulence Factors, Bordetella; D013004:Somatostatin; C043820:cyclo(7-aminoheptanoylphenylalanyl-tryptophyl-lysyl-benzylthreonyl); D002217:Carbachol; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000241:Adenosine; D007545:Isoproterenol