Cardiovascular effects induced by the stimulation of neuropeptide FF receptors in the dorsal vagal complex: an autoradiographic and pharmacological study in the rat

International audiencePrevious studies have suggested that central administration of neuropeptide FF-related peptides may modulate cardiovascular parameters in the rat. In the present study, we investigated the role of dorsal vagal complex neuropeptide FF receptors in the central regulation of cardiovascular parameters. The fate of neuropeptide FF receptors in normal and nodose ganglionectomized rats was investigated using an autoradiographic approach with 125I-[DTyr1, (NMe)Phe3]NPFF as ligand for these receptors. We showed that neuropeptide FF binding sites are preferentially located postsynaptically with respect to the vagal afferent fibers in the nucleus tractus solitarius. Thus, ganglionectomy reduced by only 30% and 17% the density of peptide binding sites in the rostral and caudal regions of this nucleus, respectively. Bilateral microinjection of neuropeptide FF (1 nmol) into the commissural nucleus tractus solitarius produced an increase in blood pressure (+13.8 +/- 0.8 mmHg, n = 6), bradycardia (-29.0 +/- 3.2 bpm) and a significant inhibition (-47.6 +/- 3.1%) of the cardiac component of the baroreceptor reflex. Further studies with doses below 1 nmol indicate that NTS microinjections of the neuropeptide produced a dose-dependent decrease in heart rate. Similar cardiovascular effects were observed after bilateral NTS microinjections of one analog neuropeptide FF receptor agonist, [DTyr1, (NMe)Phe3]NPFF (1 nmol). Pretreatment with prazosin (100 micrograms/kg), an alpha 1-adrenoreceptor antagonist, inhibited the neuropeptide FF-evoked blood pressure effect. In addition, the neuropeptide FF-induced heart rate decrease was abolished by pretreatment with atropine (30 micrograms/kg), a muscarinic receptor antagonist. Taken together, these anatomical and pharmacological data suggest that neuropeptide FF receptors within the nucleus tractus solitarius, preferentially located on the postsynaptic component, are involved in the central reflex regulation of cardiovascular parameters

Effects of neuropeptide SF and related peptides on acid sensing ion channel 3 and sensory neuron excitability

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Functional differences between NPFF1 and NPFF2 receptor coupling: High intrinsic activities of RFamide-related peptides on stimulation of [35S]GTPγS binding

International audienceBy using an optimized [(35)S]GTPgammaS binding assay, the functional activities (potency and efficacy) of peptides belonging to three members of the RFamide family; Neuropeptide FF (NPFF), prolactin-releasing peptide (PrRP) and 26RFamide, were investigated on NPFF(1) and NPFF(2) receptors stably expressed in Chinese Hamster Ovary (CHO) cells. Despite their large differences in affinity and selectivity, all analogues tested behaved as agonists toward NPFF(1) and NPFF(2) receptors. High NaCl concentration in the assay strongly increased the efficacy toward NPFF(2) receptors and augmented differences among agonists. In low sodium conditions, whereas the potencies of agonists correlated with their affinities for NPFF(1) receptors, NPFF(2) receptors exhibited an extraordinary activity since all compounds tested displayed EC(50) values of GTPgammaS binding lower than their K(I) values. Comparisons of functional values between NPFF(1) and NPFF(2) receptors revealed unexpected potent selective NPFF(2) agonists especially for the PLRFamide and the VGRFamide sequences. By using blocker peptides, we also show that Galpha(i3) and Galpha(s) are the main transducers of NPFF(1) receptors while NPFF(2) are probably coupled with Galpha(i2), Galpha(i3), Galpha(o) and Galpha(s) proteins. Our data indicate that NPPF(1) and NPFF(2) receptors are differently coupled to G proteins in CHO cells