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

• Published in: British journal of pharmacology 1993-11, Vol.110 (3), p.1156-1164
• Main Authors: Feniuk, W., Dimech, J., Humphrey, P.P.A.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Atrial Function; atrium; Biological and medical sciences; Calcium - metabolism; Depression, Chemical; Electric Stimulation; Guinea Pigs; Heart Atria - ultrastructure; ileum; Ileum - ultrastructure; Male; Medical sciences; Molecular Sequence Data; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Muscle, Smooth - ultrastructure; Myocardial Contraction - drug effects; Myocardium - ultrastructure; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Protease Inhibitors - pharmacology; Receptors, Somatostatin - antagonists & inhibitors; Receptors, Somatostatin - drug effects; Receptors, Somatostatin - physiology; Somatostatin - analogs & derivatives; Somatostatin - pharmacology; Somatostatin receptors; somatostatin14; somatostatin28; vas deferens; Vas Deferens - ultrastructure
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1993.tb13935.x

1 Somatostatin14 (SS14) 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, SS14, somatostatin28 (SS28), somatostatin25 (SS25) 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, SS28 was about 30 times more potent than SS14. However, although angiopeptin was nearly as potent as SS14 as an agonist in the vas deferens, in guinea‐pig atrium angiopeptin had low intrinsic activity and antagonized the negative inotropic action of both SS14 and SS28 (pKB values of 7.4 and 7.2, respectively). CGP 23996 was 2–7 times weaker than SS14 in guinea‐pig vas deferens and atria. 4 Phosphoramidon (1 μm) and amastatin (10 μm) did not influence the potency of SS14 or SS28 in either the guinea‐pig ileum or right atrium. In the guinea‐pig vas deferens, phosphoramidon and amastatin did not affect the potency of SS28, but enhanced the potency of SS14 about 5 fold. Despite the presence of phosphoramidon and amastatin, SS28 was still more potent than SS14 in the vas deferens. 5 The putative somatostatin receptor blocking drug, cyclo(7‐aminoheptanoyl Phe‐d‐Trp‐Lys‐Thr[Bzl]) (CPP; 1 μm), did not antagonize the effects of either SS14 or SS28 in ileum, vas deferens or atrial preparations. 6 Somatostatin14 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 SS14 was markedly and inversely related to the external Ca2+ concentration. The inhibitory effect of SS14 in guinea‐pig atrium was only partly dependent on the external Ca2+ concentration. 7 The somatostatin receptors mediating the inhibitory effect of SS14 in the ileum and vas deferens can be distinguished by the differential relative potencies of SS14 and SS28. In the former, SS14 and SS28 have similar potency whilst in the latter SS28 is m