Characterization of vascular postsynaptic NPY receptor function and regulation and differential sensitivity of Y1 and Y2 receptor function to changes in extracellular calcium availability and prior in vitro peptide exposure.
Effects of calcium-free buffer, nifedipine, or prior cumulative neuropeptide Y (NPY) receptor agonist concentration exposure on vasoconstrictive responsiveness to the agonists were assessed in norepinephrine (NE)-conditioned isolated rat femoral artery rings. Calcium-free buffer and nifedipine partially inhibited responsiveness to initial NPY exposure; residual responsiveness to NPY re-exposure was unaffected. In contrast, these treatments markedly inhibited responsiveness to the Y2 agonist NPY13-36, the calcium channel agonist BAY K 8644 (BAY) and the partial alpha 1 adrenoceptor agonist indanidine but did not alter to the Y1 agonist [Leu31,Pro34]NPY. Responsiveness to NPY and NPY13-36 but not to BAY or indanidine was markedly reduced 120 min following conditioning regardless of prior ring exposure to the same peptide; only prior exposure reduced responsiveness to [Leu31,Pro34]NPY. Responsiveness changes to NPY at various times or after various numbers of NE and/or NPY exposures indicated that pre-exposure and time-related responsiveness reductions were discriminable and temporally unrelated to conditioning. Postsynaptic vascular Y2 receptor activation therefore accounts for the known sensitivity of NPY-induced pressor and vasoconstrictive actions to nifedipine. The 'time-dependent' loss of Y2 receptor function may also explain prior failures to observe postsynaptic arterial Y2 receptors in vitro.
Tessel
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Department of Pharmacology, School of Pharmacy, University of Kansas, Lawrence 66045-2505.
Miller
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Misse
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Dong
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Doughty
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D009478:Neuropeptide Y; D010446:Peptide Fragments; D010455:Peptides; D017476:Receptors, Neuropeptide Y; D014662:Vasoconstrictor Agents; C062924:neuropeptide Y (13-36); C062259:neuropeptide Y, Leu(31)-Pro(34)-; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D003000:Clonidine; C034204:indanidine; D002118:Calcium