Modulatory interactions of neuropeptide Y (NPY) on sympathetic neurotransmission.
I. Based on experiments on the rat portal vein, it is suggested that NPY is capable of inhibiting TNS-induced release of 3H-NA from the sympathetic nerves via a prejunctional site of action, and that NPY enhances the spontaneous contractility and the vasoconstrictor response to TNS via a postjunctionally mediated mechanism. II. Based on experiments in the pithed rat, it is suggested that NPY inhibits the PNS-induced enhancement of plasma NA and A levels, and that this reflects an inhibitory effect of NPY on the release of NA from sympathetic nerve terminals and the secretion of A from the adrenal medulla. III. Based on experiments in the pithed rat, it is suggested that infusion of NPY, at subthreshold doses, potentiates the blood-pressure response to PNS and to injection of the alpha-agonist phenylephrine and that NPY in higher doses induces pressor responses, which are resistant to alpha- and beta-adrenoceptor blockade but sensitive to the calcium antagonist nifedipine. IV. Based on experiments in the pithed rat, it is suggested that A is secreted from the adrenal medulla directly into the circulating blood, since the peak plasma A level occurred immediately (0-20 s) after the initiation of PNS, and that NA and NPY are released from sympathetic nerve terminals from where the transmitters have to diffuse into the systemic circulation, since the maximal levels of circulating NA and NPY-LI were reached later (20-40 s) than A. V. Based on experiments in the pithed guinea-pig, it is suggested that the PNS-induced increase of the plasma NPY-LI level is modulated by a prejunctional alpha 2-adrenoceptor mediated inhibitory control mechanism, since the alpha 2-agonist clonidine was found to reduce and the alpha 2-antagonist yohimbine to markedly enhance the PNS-induced increase in plasma NPY-LI, whereas the alpha 1-antagonist prazosin had no effect. Furthermore, guanethidine reduced this parameter, lending further support to the assumption that circulating NPY is of sympathetic neuronal origin. VI. Based on experiments in the pithed guinea-pig, it is suggested that prejunctional facilitatory beta-adrenoceptors may also be involved in the regulation of the NPY release, since infusion of isoprenaline elicited a facilitation of the PNS-induced increase of plasma NPY-LI levels which could be antagonised by propranolol.(ABSTRACT TRUNCATED AT 400 WORDS)
Linton-Dahlöf
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Department of Clinical Pharmacology, Gothenburg University, Sweden.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology; D004558:Electric Stimulation; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010525:Peripheral Nerves / Q000187:drug effects; D011169:Portal Vein / Q000294:innervation; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D009478:Neuropeptide Y; D000804:Angiotensin II; D009638:Norepinephrine; D004837:Epinephrine