Chromodacryorrhea and repetitive hind paw tapping: models of peripheral and central tachykinin NK1 receptor activation in gerbils.
The in vivo pharmacological profiles of the selective tachykinin NK1 receptor agonists, [Sar9,Met(O2)11]substance P and GR 73632, were examined in gerbils. Both agonists induced a pronounced chromodacryorrhea following intravenous injection which was stereoselectively antagonised by the tachykinin NK1 receptor antagonist, CP-99,994, but not by its inactive enantiomer, CP-100,263, or the rat-selective tachykinin NK1 receptor antagonist, RP 67,580. In contrast, chromodacryorrhea was not observed following intravenous injection of the selective tachykinin NK2 receptor agonist, [beta-Ala8]neurokinin A-(4-10), or the selective tachykinin NK3 receptor agonist, senktide. These results suggest that [Sar9,Met(O2)11]substance P-induced chromodacryorrhea results from activation of peripheral tachykinin NK1 receptors. Repetitive hind paw tapping was also observed in gerbils but only following intracerebroventricular injection of [Sar9,Met(O2)11]substance P or GR 73632. Furthermore, GR 73632-induced hind paw tapping was significantly attenuated by co-administration of the peptide tachykinin NK1 receptor antagonist, GR 82334, or intravenous injection of CP-99,994. Thus, in contrast to chromodacryorrhea, repetitive hind paw tapping may result from activation of central tachykinin NK1 receptors.
Bristow
L J
LJ
Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Young
L
L
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005849:Gerbillinae; D006243:Harderian Gland / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D054833:Isoindoles; D008297:Male; D015288:Neurokinin A / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology
D007211:Indoles; D054833:Isoindoles; D010446:Peptide Fragments; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C062618:substance P, Sar(9)-Met(O2)(11)-; C068032:GR 73632; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; D015288:Neurokinin A