Complex effects of Gillichthys urotensin II on rat aortic strips.
The aim of this study was to determine whether the fish neuropeptide, Gillichthys urotensin II (GUII), possesses significant biological activity on rat aortic strips. On intact strips, pre-contracted by noradrenaline (100 nM), low concentrations (0.1-0.5 nM) of GUII produced relaxations, while higher concentrations (1-10 nM) caused further contraction. On strips rubbed to remove endothelial cells, relaxations were absent but contractile responses to higher concentrations of GUII remained. GUII (0.02-10 nM) produced dose-related contractions of quiescent, intact aortic strips. These contractions consisted of two components, tonic and phasic, and were potentiated in rubbed strips and in the presence of the antioxidant drug hydroquinone (10 microM). Mepacrine (40 microM) and p-bromophenacyl bromide (50 microM) completely abolished contractions to GUII, but indomethacin (10 microM) and nordihydro-guaiaretic acid (10 microM) were without effect. The phasic, but not the tonic, component of the contractile response was inhibited by nitrendipine (200 nM), and was absent in bathing medium from which Ca2+ had been omitted. Addition of EGTA (2 mM) to Ca2+-free bathing medium abolished the residual tonic component. GUII-induced contractions were completely abolished by the calmodulin antagonists trifluoperazine (50 microM) and W-7 (30 microM). It is concluded that GUII, previously considered devoid of significant activity on mammalian tissues, produces potent endothelium-dependent relaxations and endothelium-independent contractions of rat aorta, and possible mechanisms underlying each response are discussed.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D005399:Fishes; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014579:Urotensins / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D002147:Calmodulin; D018377:Neurotransmitter Agents; D010455:Peptides; D010743:Phospholipids; D014579:Urotensins; C029677:urotensin II; D002118:Calcium; D009638:Norepinephrine