Antagonist effects of seglitide (MK 678) at somatostatin receptors in guinea-pig isolated right atria.
Somatostatin (SS) exerts a negative inotropic effect in isolated atria. Here we report that in guinea-pig isolated right atria, seglitide, a potent cyclic hexapeptide somatostatin agonist, behaves as a competitive somatostatin receptor antagonist with pA2 values against SS14, SS25 and SS28, of 6.50 +/- 0.40, 6.24 +/- 0.08 and 6.09 +/- 0.06, respectively. Seglitide had little or no effect on the negative inotropic action of carbachol or N6-cyclohexyladenosine. Our findings indicate that the receptor-response coupling characteristics of guinea-pig atria are such that in this preparation seglitide has low intrinsic activity and behaves specifically as a somatostatin receptor antagonist.
Dimech
J
J
Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge.
Feniuk
W
W
Humphrey
P P
PP
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C027513:N(6)-cyclohexyladenosine; D013004:Somatostatin; C040968:seglitide; D002217:Carbachol; D000241:Adenosine