Evidence for a non-adrenoceptor, imidazoline-mediated contractile response to oxymetazoline in the porcine isolated rectal artery.
Imidazoline derivatives are known to elicit responses through both alpha(2)-adrenoceptor and non-adrenoceptor, imidazoline sites, though as yet there are no examples of the latter on vascular smooth muscle. In the presence of 0.3 microM prazosin, neither UK-14304 (0.01 - 3 microM) nor oxymetazoline (0.01 - 30 microM) caused a significant contraction of the porcine isolated rectal artery, a preparation with a low density of alpha(2)-adrenoceptors. In the presence of a combination of U46619 and forskolin, however, both agonists produced concentration-dependent contractions. Pretreatment with phenoxybenzamine (3 microM) abolished responses to UK-14304, but left those elicited by oxymetazoline largely unaffected. The putative I(3) imidazoline antagonist 2-(2,3 dihydro-2-benzofuranyl)-2-imidazole (KU-14R, 10 microM) caused a 6 fold rightward displacement of the phenoxybenzamine-insensitive concentration - response curve to oxymetazoline. Our data indicates that non-adrenoceptor, imidazoline sites, pharmacologically similar to the I(3) imidazoline site on islet cells, mediate vasoconstriction in the porcine isolated rectal artery.
Minyan
W
W
School of Biomedical Sciences, Queen's Medical Centre, Nottingham, NG7 2UH.
Dunn
W R
WR
Blaylock
N A
NA
Chan
S L
SL
Wilson
V G
VG
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D001572:Benzofurans / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D010109:Oxymetazoline / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology; D012007:Rectum / Q000098:blood supply*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D001572:Benzofurans; D007093:Imidazoles; C106086:KU 14R; D011810:Quinoxalines; D011941:Receptors, Adrenergic; D010643:Phenoxybenzamine; D005576:Colforsin; D000068438:Brimonidine Tartrate; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D010109:Oxymetazoline; D009638:Norepinephrine