Neuropeptide Y (18-36) modulates chromaffin cell catecholamine secretion by blocking the nicotinic receptor ion channel

Jialin C Zheng, R. A. Morrisett, J. Zhu, T. D. Hexum

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Neuropeptide Y (NPY) is a widely distributed peptide with varied activities including inhibition of [3H]NE secretion from chromaffin cells. In the present study, we investigated the mechanism through which NPY and NPY fragments inhibit nicotinic receptor induced influx of 22Na+ and 45Ca++ into bovine chromaffin cells. Fragments of NPY, including NPY13- 36, NPY18-36 and NPY26-36, are more potent inhibitors of 45Ca++ and 22Na+ influx than NPY. High [K+]- and BAY K 8644-induced 45Ca++ influx and veratridine-induced 22Na+ influx are not inhibited by either NPY or NPY fragments. Thus, the site of NPY or NPY fragment action is not voltage-gated Ca++ or Na+ channels. A significant amount of acetylcholine- induced 45Ca++ influx still occurs in the presence of the voltage-gated Ca++ channel blockers: nifedipine (L-type), ω-conotoxin-GVIA (N-type) and ω-agatoxin-IVA (P-type). NPY18-36, in the presence of these channel blockers, inhibited the residual nicotinic receptor-induced Ca++ influx. The response to NPY18-36 is not pertussis toxin sensitive. The rank orders of potency for inhibition of 45Ca++ and 22Na+ are the same: NPY18-36 ≥ NPY26-36 > NPY13-36 > NPY ≥ NPY(free acid). Moreover, the IC50 values for NPY18-36 inhibition of 45Ca++ influx and 22Na+ influx are similar, 0.9 x 10-6 M and 2.03 x 10-6 M, respectively. Regression analysis for inhibition of these two phenomena produced a correlation coefficient of .9697 (P < .0003). Regression analysis for inhibition of 1,1-dimethyl-4- phenylpiperizinium (DMPP)-stimulated [3H]NE secretion vs. inhibition of DMPP-stimulated 22Na+ influx produced a correlation coefficient of .9894 (P < .0001). We conclude that NPY modifies nicotinic receptor function by blocking the nicotinic receptor ligand-gated ion channel.

Original languageEnglish (US)
Pages (from-to)891-897
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume274
Issue number2
StatePublished - Jan 1 1995

Fingerprint

Chromaffin Cells
Neuropeptide Y
Nicotinic Receptors
Ion Channels
Catecholamines
neuropeptide Y (18-36)
Agatoxins
Regression Analysis
Conotoxins
Veratridine
Ligand-Gated Ion Channels
Pertussis Toxin
Nifedipine
Inhibitory Concentration 50
Acetylcholine

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Neuropeptide Y (18-36) modulates chromaffin cell catecholamine secretion by blocking the nicotinic receptor ion channel. / Zheng, Jialin C; Morrisett, R. A.; Zhu, J.; Hexum, T. D.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 274, No. 2, 01.01.1995, p. 891-897.

Research output: Contribution to journalArticle

@article{a00b572c744b47e3adea6fb470bf1bbd,
title = "Neuropeptide Y (18-36) modulates chromaffin cell catecholamine secretion by blocking the nicotinic receptor ion channel",
abstract = "Neuropeptide Y (NPY) is a widely distributed peptide with varied activities including inhibition of [3H]NE secretion from chromaffin cells. In the present study, we investigated the mechanism through which NPY and NPY fragments inhibit nicotinic receptor induced influx of 22Na+ and 45Ca++ into bovine chromaffin cells. Fragments of NPY, including NPY13- 36, NPY18-36 and NPY26-36, are more potent inhibitors of 45Ca++ and 22Na+ influx than NPY. High [K+]- and BAY K 8644-induced 45Ca++ influx and veratridine-induced 22Na+ influx are not inhibited by either NPY or NPY fragments. Thus, the site of NPY or NPY fragment action is not voltage-gated Ca++ or Na+ channels. A significant amount of acetylcholine- induced 45Ca++ influx still occurs in the presence of the voltage-gated Ca++ channel blockers: nifedipine (L-type), ω-conotoxin-GVIA (N-type) and ω-agatoxin-IVA (P-type). NPY18-36, in the presence of these channel blockers, inhibited the residual nicotinic receptor-induced Ca++ influx. The response to NPY18-36 is not pertussis toxin sensitive. The rank orders of potency for inhibition of 45Ca++ and 22Na+ are the same: NPY18-36 ≥ NPY26-36 > NPY13-36 > NPY ≥ NPY(free acid). Moreover, the IC50 values for NPY18-36 inhibition of 45Ca++ influx and 22Na+ influx are similar, 0.9 x 10-6 M and 2.03 x 10-6 M, respectively. Regression analysis for inhibition of these two phenomena produced a correlation coefficient of .9697 (P < .0003). Regression analysis for inhibition of 1,1-dimethyl-4- phenylpiperizinium (DMPP)-stimulated [3H]NE secretion vs. inhibition of DMPP-stimulated 22Na+ influx produced a correlation coefficient of .9894 (P < .0001). We conclude that NPY modifies nicotinic receptor function by blocking the nicotinic receptor ligand-gated ion channel.",
author = "Zheng, {Jialin C} and Morrisett, {R. A.} and J. Zhu and Hexum, {T. D.}",
year = "1995",
month = "1",
day = "1",
language = "English (US)",
volume = "274",
pages = "891--897",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - Neuropeptide Y (18-36) modulates chromaffin cell catecholamine secretion by blocking the nicotinic receptor ion channel

AU - Zheng, Jialin C

AU - Morrisett, R. A.

AU - Zhu, J.

AU - Hexum, T. D.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - Neuropeptide Y (NPY) is a widely distributed peptide with varied activities including inhibition of [3H]NE secretion from chromaffin cells. In the present study, we investigated the mechanism through which NPY and NPY fragments inhibit nicotinic receptor induced influx of 22Na+ and 45Ca++ into bovine chromaffin cells. Fragments of NPY, including NPY13- 36, NPY18-36 and NPY26-36, are more potent inhibitors of 45Ca++ and 22Na+ influx than NPY. High [K+]- and BAY K 8644-induced 45Ca++ influx and veratridine-induced 22Na+ influx are not inhibited by either NPY or NPY fragments. Thus, the site of NPY or NPY fragment action is not voltage-gated Ca++ or Na+ channels. A significant amount of acetylcholine- induced 45Ca++ influx still occurs in the presence of the voltage-gated Ca++ channel blockers: nifedipine (L-type), ω-conotoxin-GVIA (N-type) and ω-agatoxin-IVA (P-type). NPY18-36, in the presence of these channel blockers, inhibited the residual nicotinic receptor-induced Ca++ influx. The response to NPY18-36 is not pertussis toxin sensitive. The rank orders of potency for inhibition of 45Ca++ and 22Na+ are the same: NPY18-36 ≥ NPY26-36 > NPY13-36 > NPY ≥ NPY(free acid). Moreover, the IC50 values for NPY18-36 inhibition of 45Ca++ influx and 22Na+ influx are similar, 0.9 x 10-6 M and 2.03 x 10-6 M, respectively. Regression analysis for inhibition of these two phenomena produced a correlation coefficient of .9697 (P < .0003). Regression analysis for inhibition of 1,1-dimethyl-4- phenylpiperizinium (DMPP)-stimulated [3H]NE secretion vs. inhibition of DMPP-stimulated 22Na+ influx produced a correlation coefficient of .9894 (P < .0001). We conclude that NPY modifies nicotinic receptor function by blocking the nicotinic receptor ligand-gated ion channel.

AB - Neuropeptide Y (NPY) is a widely distributed peptide with varied activities including inhibition of [3H]NE secretion from chromaffin cells. In the present study, we investigated the mechanism through which NPY and NPY fragments inhibit nicotinic receptor induced influx of 22Na+ and 45Ca++ into bovine chromaffin cells. Fragments of NPY, including NPY13- 36, NPY18-36 and NPY26-36, are more potent inhibitors of 45Ca++ and 22Na+ influx than NPY. High [K+]- and BAY K 8644-induced 45Ca++ influx and veratridine-induced 22Na+ influx are not inhibited by either NPY or NPY fragments. Thus, the site of NPY or NPY fragment action is not voltage-gated Ca++ or Na+ channels. A significant amount of acetylcholine- induced 45Ca++ influx still occurs in the presence of the voltage-gated Ca++ channel blockers: nifedipine (L-type), ω-conotoxin-GVIA (N-type) and ω-agatoxin-IVA (P-type). NPY18-36, in the presence of these channel blockers, inhibited the residual nicotinic receptor-induced Ca++ influx. The response to NPY18-36 is not pertussis toxin sensitive. The rank orders of potency for inhibition of 45Ca++ and 22Na+ are the same: NPY18-36 ≥ NPY26-36 > NPY13-36 > NPY ≥ NPY(free acid). Moreover, the IC50 values for NPY18-36 inhibition of 45Ca++ influx and 22Na+ influx are similar, 0.9 x 10-6 M and 2.03 x 10-6 M, respectively. Regression analysis for inhibition of these two phenomena produced a correlation coefficient of .9697 (P < .0003). Regression analysis for inhibition of 1,1-dimethyl-4- phenylpiperizinium (DMPP)-stimulated [3H]NE secretion vs. inhibition of DMPP-stimulated 22Na+ influx produced a correlation coefficient of .9894 (P < .0001). We conclude that NPY modifies nicotinic receptor function by blocking the nicotinic receptor ligand-gated ion channel.

UR - http://www.scopus.com/inward/record.url?scp=0029145211&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029145211&partnerID=8YFLogxK

M3 - Article

C2 - 7543575

AN - SCOPUS:0029145211

VL - 274

SP - 891

EP - 897

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 2

ER -