Neuropeptide Y inhibition of nicotinic receptor-mediated chromaffin cell secretion

T. D. Hexum, J. Zheng, J. Zhu

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12 Scopus citations

Abstract

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 ≥ NPY26-36 > NPY13-36. NPY and NPY(free 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.

Original languageEnglish (US)
Pages (from-to)61-66
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume271
Issue number1
StatePublished - 1994

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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