Somatostatin-induced contraction of human isolated saphenous vein involves sst2 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 EC50 value of approximately 20 nM. The peptidase inhibitors phosphoramidon and amastatin did not alter the potency of SRIF. The sst2 receptor-selective peptide BIM-23027 was approximately three times more potent than SRIF in contracting the vein, whereas the sst5 receptor-selective peptide L-362855 was approximately 50 times weaker. The sst3 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-D Trp-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 EC50 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 sst2 receptor. The receptor transduction mechanism appears to involve activation of L-type calcium channels and entry of extracellular calcium.
Dimech
J
J
Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge, England.
Feniuk
W
W
Latimer
R D
RD
Humphrey
P P
PP
D000368:Aged; D000595:Amino Acid Sequence; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D015282:Octreotide / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000502:physiology*; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D015220:Calcium Channels; D017481:Receptors, Somatostatin; D013004:Somatostatin; D015282:Octreotide