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Shaw AM, Bunton DC, Brown T, Irvine J, MacDonald A: Regulation of sensitivity to 5-hydroxytryptamine in pulmonary supernumerary but not conventional arteries by a 5-HT (1D)-like receptor. Eur J Pharmacol. 2000 Nov 10;408(1):69-82.
Bovine pulmonary supernumerary arteries are more sensitive to 5-hydroxtryptamine (5-HT) (pD (2) 6.43+/-0.25) than conventional arteries (pD (2) 5.32+/-0.16). This study investigated receptors for 5-HT in ring segments of these arteries. The 5-HT (2) receptor agonist, 2,5 dimethoxy-4-iodoamphetamine hydrobromide (DOI) constricts both arteries. The selective 5-HT (2) receptor antagonist ritanserin produced insurmountable antagonism of 5-HT concentration-response curves in both arteries, whereas the 5-HT (1B/1D) receptor antagonist N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'(5-methyl- 1,2,4-oxadiazol-3-yl [1,1,-biphenyl]-4-carboxamide hydrochloride (GR127935) produced much greater antagonism in supernumerary arteries. In rings preconstricted with 9,11-dideoxy-9, 11-methanoepoxy prostalagdin F (2alpha) (U46619) and relaxed with the adenylyl cyclase activator forskolin, the selective 5-HT (ID) receptor agonist 2-[5-[3-(4-methylsulphonylamino) benzyl-1,2, 4-oxadiazol-5-yl]-1H-indole-3-yl] ethylamine (L694247) reversed the relaxation. Concentration-response curves for L694247-induced reversal of forskolin-relaxation were antagonised by GR127935 in supernumerary (pK (B) 8.6) and conventional (pK (B) 8.4) arteries, whereas concentration-response curves to 5-HT-were less sensitive to antagonism by GR127935T and this was more obvious in conventional (pK (B) 7.6) than supernumerary (pK (B) 8.1) arteries. Neither the selective 5-HT (1D) receptor antagonist (1-(3-chlorophenyl)-4-[3, 3-diphenyl (2-(S,R) hydroxypropanyl) piperazine] hydrochloride (BRL15572) nor the 5-HT (1B) receptor antagonist (2,3,6, 7-tetrahydro-1'-methyl-5-[2'methyl-4'5-(methyl-1,2,4-oxadiazol-3-y l) biphenyl-4-carbonyl] furo [2,3-f] indole-3-spiro-4'-piperidine hydrochloride (SB224289) antagonised concentration-response curves induced by 5-HT or 5-HT (1)-receptor-selective agonists. In addition to the 5-HT (2A) receptor, 5-HT activates a GR127935-sensitive and a GR127935-insensitive receptor in these arteries. Supernumerary arteries have a greater proportion of GR127935-sensitive receptors, which display only some of the pharmacological characteristics of the cloned 5-HT (ID) receptor. It is possible that the GR127935-sensitive receptor could be a species homologue of the human 5-HT (1B) receptor that is insensitive to SB224289. |
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