Neuropeptide Y inhibition of nicotinic receptor-mediated chromaffin cell secretion.
Neuropeptide Y (NPY), a widely distributed peptide with varied activities, inhibits nicotinic receptor-induced [3H]norepinephrine ([3H]NE) secretion from bovine chromaffin cells. The secretion produced by membrane depolarization with high KCl concentrations or veratridine is not inhibited. Fragments of NPY, such as NPY18-36, are potent inhibitors of [3H]NE secretion, whereas [Leu31,Pro34]-NPY and peptide YY have no effect. The response to NPY18-36 is not sensitive to pertussis toxin pretreatment of chromaffin cells. NPY fragments also inhibit nicotinic receptor-induced 45Ca++ influx but not that induced by KCl or veratridine. The rank orders of potency for inhibition of [3H]NE secretion and 45Ca++ influx are the same: NPY18-36 > or = NPY26-36 > NPY13-36. NPY and NPYfree acid are weak inhibitors of secretion but not 45Ca++ influx. Moreover, the IC50s for NPY18-36 inhibition of [3H]NE secretion and 45Ca++ influx are comparable, 1.4 x 10(-6) M and 0.9 x 10(-6) M, respectively. Regression analysis produced a correlation coefficient of 0.9842 (P < .0001). It was concluded that NPY inhibits [3H]NE secretion by a modification of the nicotinic receptor-mediated increase in Ca++ influx. The characterization of the response suggests that the NPY effect is mediated by a previously undefined NPY receptor subtype that was designated Y4.
Department of Pharmacology, University of Nebraska Medical Center, Omaha.
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000378:metabolism*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D009478:Neuropeptide Y / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology
D009478:Neuropeptide Y; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; C059889:neuropeptide Y (18-36); D004246:Dimethylphenylpiperazinium Iodide; D002118:Calcium; D009638:Norepinephrine