Somatostatin-induced contraction mediated by endothelial TXA2 production in canine cerebral arteries.
Whether somatostatin causes endothelium-dependent contraction (EDC) in isolated canine basilar arteries was examined. Somatostatin (10(-8)-10(-6) M) caused transient contractions in a dose-dependent manner. These contractions were abolished by removal of the endothelium, while the contractile response to neuropeptide Y occurred even after removal of the endothelium. The EDC induced by somatostatin (10(-7) M) was affected by neither atropine (10(-6) M) nor cyclo-somatostatin (10(-5) M), which suggests that the EDC is not due to release of endogenous acetylcholine and that the endothelial somatostatin receptor is different from hormonal somatostatin receptors. The somatostatin-induced EDC was attenuated by cyclooxygenase inhibitors (aspirin and indomethacin), thromboxane A2 (TXA2) synthetase inhibitors (OKY-064 and RS-5186), and TXA2 antagonists (ONO-3708 and S-145), which suggests that the endothelium-derived contracting factor is TXA2. These findings demonstrate that somatostatin causes EDC via activation of TXA2 synthesis in canine cerebral arteries.
Shirahase
H
H
Research Laboratories, Kyoto Pharmaceutical Industries, Ltd., Japan.
Kanda
M
M
Shimaji
H
H
Usui
H
H
Rorstad
O P
OP
Kurahashi
K
K
D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D013004:Somatostatin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D013004:Somatostatin; D013928:Thromboxane A2; C017783:somatostatin, Trp(8)-; D013930:Thromboxane-A Synthase