Cardiovascular and behavioural effects of centrally administered neuropeptide K in the rat: receptor characterization.
1. The cardiovascular and behavioural responses to intracerebroventricularly (i.c.v.) administered neuropeptide K (NPK) were studied in conscious rats. The central effects of NPK were characterized by pretreatment (i.c.v.) with selective antagonists for the NK1 ((+/-)-CP 96345 and RP 67580), NK2 (SR 48968) and NK3 (R 487) receptors. 2. NPK (10-65 pmol) induced tachycardia and dose-dependent increases of mean arterial blood pressure. The cardiovascular responses reached a maximum within 3 min post-injection and lasted for more than 1 h. Concurrently, NPK produced dose-dependent increases of face washing, head scratching, grooming, walking and wet dog shakes. 3. A desensitization of most of the behavioural responses (except head scratching) but not of the cardiovascular response was shown when two consecutive injections of 25 pmol NPK were given 24 h apart. 4. Both the cardiovascular and behavioural responses (except the head scratching) to 25 pmol NPK were blocked by pre-administration (i.c.v.) of 6.5 nmol (+/-)-CP 96345 or RP 67580 given 5 min earlier. No inhibition of NPK responses was observed when 6.5 nmol SR 48968 or R 487 were used in a similar study. Additionally, NPK effects were significantly reduced 24 h after the prior injection of (+/-)-CP 96345 but not of RP 67580. 5. These results support the involvement of NK1 receptors in the cardiovascular and behavioural effects of i.c.v. NPK. Thus, this peptide may play a putative role in central cardiovascular regulation as it is the most potent endogenous tachykinin described centrally, to date.
Prat
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Department of Physiology, Faculty of Medicine, Université de Montréal, Québec, Canada.
Picard
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P
Couture
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R
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D054833:Isoindoles; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D013373:Substance P / Q000037:antagonists & inhibitors; D015320:Tachykinins
D001713:Biphenyl Compounds; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D009479:Neuropeptides; D009842:Oligopeptides; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018013:Receptors, Neuropeptide; D015320:Tachykinins; C045206:neuropeptide K; C083382:R 487; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; C066892:CP 96345