Neuropeptide Y enhances ATP-induced formation of inositol phosphates in chromaffin cells.
Bovine chromaffin cells contain high affinity NPY binding sites coupled through a pertussis toxin-sensitive G protein to inhibition of cAMP accumulation. NPY alone does not alter [3H]inositol phosphate formation from [3H]phosphoinositides in these cells. Increasing NPY concentrations, in the presence of ATP (300 microM), produced a dose-dependent enhancement in [3H]-inositol phosphate formation, EC50 = 3.2 nM. Inclusion of the selective NPY-Y1 receptor antagonist BW1229 (1 microM) produced a marked decrease in NPY potency (EC50 = 3.3 microM). The Y1 receptor agonist, [Leu31, Pro34]-NPY, was equally effective with NPY, whereas NPY18-36, a Y2 receptor agonist, was much less effective. Inclusion of NPY with ATP also produced an enhancement in the release of intracellular Ca2+. The ability of NPY to enhance both [3H]inositol phosphate formation and the release of intracellular Ca2+ was pertussis toxin-insensitive. NPY action on bovine chromaffin cell receptor(s) appears to facilitated by different G proteins: one which can inhibit cAMP accumulation via a pertussis toxin-sensitive process and another which can enhance ATP activation of the inositol phosphate signaling pathway by a pertussis toxin-insensitive process.
Zheng
J
J
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260, USA.
Zhang
P
P
Toews
M
M
Hexum
T D
TD
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000378:metabolism*; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007295:Inositol Phosphates; D009478:Neuropeptide Y; D010446:Peptide Fragments; D010566:Virulence Factors, Bordetella; C059889:neuropeptide Y (18-36); C062259:neuropeptide Y, Leu(31)-Pro(34)-; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin