Pressor and tachycardic responses to intrathecal administration of neuropeptide FF in anesthetized rats.
Neuropeptide FF (NPFF) belongs to a neuropeptide family including two precursors (pro-NPFF(A) and pro-NPFF(B)) and two receptors (NPFF(1) and NPFF(2)). NPFF and NPFF receptor mRNAs have been reported to be highly expressed and localized in the rat and human spinal cord. In the present study, the i.t. action of NPFF system on blood pressure and heart rate were examined using NPFF and two related agonists, NPVF and dNPA, which exhibit highest selectivities for NPFF(1) and NPFF(2) receptors, respectively. In urethane-anesthetized rats, NPFF and related peptides (5-40 nmol, i.t.) produced significant pressor and tachycardic responses at the spinal cord level. These effects were dose-dependent and similar with respect to time-course for the three peptides. Furthermore, i.t. injection of RF9 (20 nmol), a selective NPFF antagonist, significantly antagonized the cardiovascular responses to 20 nmol NPFF and related peptides (i.t.). Moreover, pretreatment of the rats with alpha-adrenoceptor antagonist phentolamine (1mg/kg, i.v.) significantly reduced the pressor effects of NPFF. Nevertheless, pretreatment with muscarinic receptor and adrenoceptor antagonists (i.v.) could block the tachycardic effects induced by NPFF. Collectively, our results suggested that i.t. administration of NPFF and related peptides increased MAP and HR which were possibly mediated by the activation of both NPFF(1) and NPFF(2) receptors in the rat spinal cord. In addition, our results showed that the muscarinic receptor and adrenoceptor participated in the tachycardic response to i.t. NPFF, while alpha-adrenoceptor played an important role in the regulation of pressor effect of NPFF.
Fang
Quan
Q
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Medicine, and Institute of Biochemistry and Molecular Biology, School of Life Sciences, and State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, PR China.
Li
Ning
N
Jiang
Tian-nan
TN
Liu
Qian
Q
Li
Yu-lin
YL
Wang
Rui
R
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000317:Adrenergic alpha-Antagonists; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D018727:Muscarinic Antagonists; D009292:Narcotic Antagonists; D009842:Oligopeptides; D001285:Atropine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D011433:Propranolol; D010646:Phentolamine