The actions of medetomidine may not be mediated exclusively by alpha 2-adrenoceptors in the equine saphenous vein.
Spirals of endothelially denuded equine saphenous vein were used to study the pre- and post-junctional effects of medetomidine in vitro. The pD2 values were calculated for noradrenaline (6.7 +/- 0.1), phenylephrine (5.6 +/- 0.1), BHT 920 (6.2 +/- 0.2) and UK 14304 (5.7 +/- 0.2). Medetomidine produced a biphasic response, with a pD(2)1 of 8.2 +/- 0.1 and a pD(2)2 of 5.7 +/- 0.1 in the equine saphenous vein (n = 6). Prazosin (10(-7) M) significantly shifted the second phase of the medetomidine concentration-response curve to the right (pD(2)1 was 8.1 +/- 0.2 and pD(2)2 was 5.0 +/- 0.2, P < 0.05). Rings of equine saphenous vein were electrically stimulated to investigate the pre-junctional effects of medetomidine. Increasing concentrations of the alpha 2-adrenoceptor agonist BHT 920 reduced the response to electrical stimulation in a concentration dependent manner to a maximum of 40 +/- 5%, whereas medetomidine (0.1-100 nM) caused a concentration dependent enhancement to a maximum of 490 +/- 150%. These results suggest alpha 1- and alpha 2-adrenoceptors are functional in the equine saphenous vein, but that medetomidine is not acting exclusively as an alpha 2-adrenoceptor agonist.
Bryant
C E
CE
Department of Large Animal Medicine and Surgery, Royal Veterinary College, University of London, Hatfield, Herts, UK.
Clarke
K W
KW
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005260:Female; D006736:Horses; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013329:Structure-Activity Relationship
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001381:Azepines; D007093:Imidazoles; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D010656:Phenylephrine; D000068438:Brimonidine Tartrate; C024763:talipexole; D020926:Medetomidine; D009638:Norepinephrine; D011224:Prazosin