Inhibitory effect of NCO-650 on the contractile response of guinea pig ileum to some agonists

Abstract

The effect of NCO-650 on the contractile response to acetylcholine (ACh), histamine and BaCl2 was investigated using isolated guinea pig ileum. NCO-650(3×10−6 M,1×10−5M and 3×10−5m) caused a parallel shift to the right of the dose-response curve of ACh. The regression between log(DR-l) and log(B) was found to be liner with a slope of 1.04 and the estimated apparent Kg was 2.74×10−6m which is equvalent to pA2 of 5.74.NCO-650 also acts like a competitive antagonist of histamine (H1-receptor) because NCO-650 caused a parallel shift to the right of the dose-response curve for histamine(KB=5.34×10−6m;pA2=5.40,Slope= 1.09). On the other hand, a high concentration of NCO-650(1×10-4M) depressed the maximum contractions to ACh and histamine. Dose-response curve for BaCl2 was non-competitively antagonized by NCO-650 at 3×10−6m(pD2=4.21). NCO-650 dose-dependently inhibited the twitch response of the ileum to electrical stimulation at 0.1Hz. In the K-depolarized preparation, NCO-650(3×10-5M-3×10−4M) depressed the maximum contraction of the dose-response curve for CaCl2 (pD2=4.00). These results suggest that low concentrations of NCO-650 act as a competitive antagonist of muscarinic receptor and H1-receptor in guinea pig ileum, while high concentrations of NCO-650 inhibit the contractile response to ACh and histamine by reducing the release from membrane-bound Ca ion.