Characterization of somatostatin receptors in guinea‐pig isolated ileum, vas deferens and right atrium

1 Somatostatin 14 (SS 14 ) inhibits neurogenically mediated contractile responses in guinea‐pig ileum and vas deferens and exerts a direct negative inotropic action in guinea‐pig spontaneously beating right atrium. In this study, the receptors mediating these inhibitory effects have been characterized by comparing the potencies of several cyclic somatostatin analogues. 2 In the guinea‐pig ileum, SS 14 , somatostatin 28 (SS 28 ), somatostatin 25 (SS 25 ) and several smaller cyclic somatostatin analogues including octreotide, angiopeptin and CGP 23996, inhibited neurogenically mediated contractile responses, each being of similar potency. 3 In contrast, in the guinea‐pig vas deferens and right atrium, SS 28 was about 30 times more potent than SS 14 . However, although angiopeptin was nearly as potent as SS 14 as an agonist in the vas deferens, in guinea‐pig atrium angiopeptin had low intrinsic activity and antagonized the negative inotropic action of both SS 14 and SS 28 (p K B values of 7.4 and 7.2, respectively). CGP 23996 was 2–7 times weaker than SS 14 in guinea‐pig vas deferens and atria. 4 Phosphoramidon (1 μ m ) and amastatin (10 μ m ) did not influence the potency of SS 14 or SS 28 in either the guinea‐pig ileum or right atrium. In the guinea‐pig vas deferens, phosphoramidon and amastatin did not affect the potency of SS 28 , but enhanced the potency of SS 14 about 5 fold. Despite the presence of phosphoramidon and amastatin, SS 28 was still more potent than SS 14 in the vas deferens. 5 The putative somatostatin receptor blocking drug, cyclo(7‐aminoheptanoyl Phe‐ d ‐Trp‐Lys‐Thr[Bzl]) (CPP; 1 μ m ), did not antagonize the effects of either SS 14 or SS 28 in ileum, vas deferens or atrial preparations. 6 Somatostatin 14 did not modify the contractile action of carbachol or α,β‐methylene ATP in the ileum and vas deferens respectively, suggesting that the site of the inhibitory effects on neurogenically mediated contractile responses in both preparations was pre‐junctional. Consistent with this conclusion was the observation that the inhibitory effect of SS 14 was markedly and inversely related to the external Ca 2+ concentration. The inhibitory effect of SS 14 in guinea‐pig atrium was only partly dependent on the external Ca 2+ concentration. 7 The somatostatin receptors mediating the inhibitory effect of SS 14 in the ileum and vas deferens can be distinguished by the differential relative potencies of SS 14 and SS 28 . In the former, SS 14 and SS 28 have similar potency whilst in the latter SS 28 is much more potent. In this respect, the somatostatin receptor mediating negative inotropy in the guinea‐pig right atrium appears similar to that identified in the vas deferens. 8 We suggest that the somatostatin receptor mediating inhibition of neurogenic contraction in the ileum is similar to the recently cloned SSTR 2 receptor. In contrast, the somatostatin receptor mediating negative inotropy in the atrium and inhibition of neurotransmission in the vas deferens appears similar to the SSTR 4 receptor which recognises SS 28 with higher affinity than SS 14 .