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Intracerebroventricular responses to neuropeptide γ in the conscious rat: characterization of its receptor with selective antagonists
Author(s) -
Picard Pierre,
Couture Réjean
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15183.x
Subject(s) - neuropeptide , neuroscience , receptor , neuropeptide y receptor , chemistry , biology , endocrinology , pharmacology , medicine
1 The cardiovascular and behavioural effects elicited by the intracerebroventricular (i.c.v.) administration of neuropeptide γ (NPγ) in the conscious rat were assessed before and 5 min after i.c.v. pretreatment with antagonists selective for NK 1 (RP 67,580), NK 2 (SR 48,968) and NK 3 (R 820) receptors. In addition, the central effects of NPγ before and after desensitization of the NK 1 and NK 2 receptors with high doses of substance P (SP) and neurokinin A (NKA) were compared. 2 Intracerebroventricular injection of NPγ (10–780 pmol) evoked dose‐ and time‐dependent increases in mean arterial blood pressure (MAP), heart rate (HR), face washing, head scratching, grooming and wet‐dog shake behaviours. Similar injection of vehicle or 1 pmol NPγ had no significant effect on those parameters. 3 The cardiovascular and behavioural responses elicited by NPγ (25 pmol) were significantly and dose‐dependently reduced by pretreatment with 650 pmol and 6.5 nmol of SR 48,968. No inhibition of NPγ responses was observed when 6.5 nmol of RP 67,580 was used in a similar study. Moreover, the prior co‐administration of SR 48,968 (6.5 nmol) and RP 67,580 (6.5 nmol) with or without R 820 (6.5 nmol) did not reduce further the central effects of NPγ and significant residual responses (30–50%) remained. 4 No tachyphylaxis to NPγ‐induced cardiovascular and behavioural changes was observed when two consecutive injections of 25 pmol NPγ were given 24 h apart. 5 Simultaneous NK 1 and NK 2 receptor desensitization reduced significantly central effects mediated by 25 pmol NPγ. However, significant residual responses persisted as seen after pretreatment with SR 48,968. 6 The results suggest that the central effects of NPγ are mediated partly by NK 2 receptors and by another putative tachykinin receptor subtype (NPγ receptor?) that appears to be different from NK 1 and NK 3 receptors.