SOMATOSTATIN-INDUCED CONTRACTION OF HUMAN ISOLATED SAPHENOUS-VEIN INVOLVES SST(2) RECEPTOR-MEDIATED ACTIVATION OF L-TYPE CALCIUM CHANNELS

A range of somatostatin (SRIF) analogues have been used to characterize the SRIF receptor-mediating contraction of the human saphenous vein. SRIF produced concentration-dependent contractions with an EC(50) value of similar to 20 nM, The peptidase inhibitors phosphoramidon and amastatin did not alter the potency of SRIF. The sst(2) receptor-selective peptide BIM-23027 was approximately three times more potent than SRIF in contracting the vein, whereas the sst(5) receptor-selective peptide L-362855 was similar to 50 times weaker. The sst(3) receptor-selective peptide BIM-23056 did not contract the saphenous vein. Contractions to SRIF were not antagonised by the putative SRIF receptor blocker cyclo(7-aminoheptanoyl-Phe-DTrp-Lys-Thr[Bzl]) (CPP), phentolamine, or indomethacin. Decreasing the external calcium concentration reduced the maximum contraction to SRIF in a concentration-dependent manner without altering the EC(50) value. Nifedipine and verapamil also markedly reduced the SRIF-induced contraction. SRIF and several SRIF analogues caused contraction of the human saphenous vein by what appeared to be a direct effect on the smooth muscle. Their relative potencies suggest that their effects were mediated by a somatostatin receptor that is like the recombinant sst, receptor. The receptor transduction mechanism appears to involve activation of L-type calcium channels and entry of extracellular calcium.