Neuropeptide Y (18-36) modulates chromaffin cell catecholamine secretion by blocking the nicotinic receptor ion channel.
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), omega-conotoxin-GVIA (N-type) and omega-agatoxin-IVA (P-type). NPY18-36, in the presence of these channel blockers, inhibited the residual nicotinic receptor-induced Ca++ influx. The response to NPY 18-36 is not pertussis toxin sensitive. The rank orders of potency for inhibition of 45Ca++ and 22Na+ are the same: NPY18-36 > or = NPY26-36 > NPY13-36 > NPY13-36 > NPY > or = NPYfree 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Zheng
J
J
Department of Pharmacology, University of Nebraska Medical Center, Omaha, USA.
Morrisett
R A
RA
Zhu
J
J
Hexum
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TD
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000187:drug effects* / Q000378:metabolism; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D009478:Neuropeptide Y / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D037342:Pertussis Toxin; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007473:Ion Channels; D009478:Neuropeptide Y; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; D015222:Sodium Channels; D010566:Virulence Factors, Bordetella; C059889:neuropeptide Y (18-36); D004246:Dimethylphenylpiperazinium Iodide; D012964:Sodium; D037342:Pertussis Toxin; D002118:Calcium; D009638:Norepinephrine