Cardiovascular effects of intravenous administered 26RFa, a novel RFamide peptide ligand for GPR103, in anaesthetised rats.
26RFa, a novel RFamide-related peptide, has been identified as the endogenous ligand for GPR103, and the biological functions of this neuropeptide have not been well investigated. In the present study, the cardiovascular effects of intravenous administration of rat/mouse 26RFa were tested in rats. Intravenous administered 26RFa (100-800 nmol/kg, i.v.) caused a biphasic change in blood pressure, and an increase in heart rate in urethane-anaesthetised rats. The pressor effects induced by 26RFa were significantly inhibited by pretreatment with the alpha- and beta-adrenoreceptor antagonists. In contrast, the tachycardiac responses to 26RFa were significantly attenuated by bilateral cervical vagotomy and beta-adrenoreceptor antagonist propranolol. These data imply that the peripheral cardiovascular regulation of 26RFa might be involved in vagal components and catecholaminergic pathway. Furthermore, in order to evaluate the importance of the regions of 26RFa molecule in its cardiovascular regulation, the two C-terminal fragments of rat/mouse 26RFa, 26RFa(8-26) and 26RFa(19-26), were synthesized and investigated to address their peripheral cardiovascular responses in rats. Surprisingly, intravenous injections of 26RFa(8-26) and 26RFa(19-26) (50-300 nmol/kg, i.v.) produced dose-dependent increases in blood pressure and heart rate, which exerted different sensitivities to bilateral vagotomy and beta-adrenergic receptor antagonist. The results indicate that intravenous administrations of 26RFa and its fragments induced their cardiovascular effects via different pathways, which further suggest that the N-terminal residues of 26RFa are required for its cardiovascular activities.
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, Lanzhou, PR China.
Liu
Qian
Q
Li
Ning
N
Jiang
Tian-Nan
TN
Li
Yu-Lin
YL
Yan
Xiang
X
Wang
Rui
R
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008024:Ligands; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D014520:Urethane; D014628:Vagotomy
D018674:Adrenergic Antagonists; D008024:Ligands; D009479:Neuropeptides; D010446:Peptide Fragments; C516486:Qrfpr protein, rat; D043562:Receptors, G-Protein-Coupled; C480638:prepro-26RFa protein, human; D014520:Urethane