title: Tachykinin NK1 receptors mediate both vasoconstrictor and vasodilator responses in the rabbit isolated jugular vein.
abstract: We have characterized the receptor(s) mediating contraction and relaxation produced by tachykinins in the rabbit isolated jugular vein. The tachykinin NK1 receptor-selective agonists septide and [Pro9]substance P produced concentration-dependent contractions which were potentiated by either the removal of the vascular endothelium (Emax = +106% and +72%, respectively) or by pretreatment with L-nitroarginine (100 microM; 60 min before) (Emax = +123% and +71%, respectively). The tachykinin NK1 receptor-selective antagonist, (+/-)-CP-96,345 ([2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1- azabicyclo[2,2,2]octan-3-amine]) (10-300 nM) competitively antagonized septide (pKB = 9.0) with 10-fold greater potency than [Pro9]substance P (pKB = 8.0). In preparations with intact endothelium both septide and [Pro9]substance P (from 0.1 to 100 nM) relaxed the noradrenaline-(10 microM) induced tone, and their effects were markedly reduced by (+/-)-CP-96,345 (100 nM). In noradrenaline-precontracted veins L-nitroarginine (100 microM) reversed the tachykinin-induced vasodilation into a contraction, providing evidence for the involvement of nitric oxide in this response. The tachykinin NK3 and NK2 receptor-selective agonists senktide and [beta Ala8]neurokinin A-(4-10) were either ineffective, or produced small effects antagonized by (+/-)-CP-96,345 (100 nM), respectively. In conclusion, tachykinin NK1 receptors mediate both tachykinin-induced contraction and relaxation in the rabbit jugular vein. This preparation, deprived of the endothelium or pretreated with L-nitroarginine, is suitable for evaluating tachykinin agonists or antagonists.
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004727:Endothelium; D007601:Jugular Veins / Q000187:drug effects*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011817:Rabbits; D018039:Receptors, Tachykinin / Q000187:drug effects*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D014661:Vasoconstriction; D014664:Vasodilation
chemical_list: D010446:Peptide Fragments; D018039:Receptors, Tachykinin; D015320:Tachykinins; D013373:Substance P; C054725:septide; D011761:Pyrrolidonecarboxylic Acid