TY - JOUR
T1 - Neuropeptide Y inhibition of nicotinic receptor-mediated chromaffin cell secretion
AU - Hexum, T. D.
AU - Zheng, J.
AU - Zhu, J.
PY - 1994
Y1 - 1994
N2 - 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.
AB - 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.
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M3 - Article
C2 - 7965758
AN - SCOPUS:0027938085
VL - 271
SP - 61
EP - 66
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
SN - 0022-3565
IS - 1
ER -