Neuropeptide Y-ATP interactions and release at the vascular neuroeffector junction.
1. The ability of neuropeptide Y (NPY) to potentiate the contractile effect of ATP was examined using the perfused mesenteric arterial bed as a model of the vascular neuroeffector junction. 2. NPY (10(-9)-10(-7) M) and the NPY-Y1 selective agonist, Leu31Pro34 NPY (10(-9)-10(-7) M) both produced a concentration dependent potentiation of the ATP (1 and 3 mM) induced increase in perfusion pressure while the NPY-Y2 selective agonist, NPY 14-36 did not. 3. The NPY-Y1 selective antagonist BIBP 3226 (10-100 nM) produced a significant concentration dependent blockade of the Leu31Pro34 NPY (30 nM) induced potentiation of the ATP (3 mM) induced increase in perfusion pressure. These results are consistent with the NPY-induced potentiation of ATP effect being due to activation of the NPY-Y1 receptor subtype. 4. Periarterial nerve stimulation (supramaximal voltage, 8 and 16 Hz, 30s caused a release of ATP, as well as metabolites, from the perfused mesenteric arterial bed. KCl evoked (50 mM, 5 min) release of ATP from nerve growth factor (NGF) differentiated PC12 cells. 5. Endothelin-1 (ET-1) produced a concentration dependent (10(-15)-10(-8) M) inhibition of the K-1-evoked release of ATP from NGF-differentiated PC12 cells. This effect was mimicked by the selective ETB agonists, BQ 3020, STX-6C and IRL 1620. The ETA/ETB antagonist PD142893 blocked the inhibitory effect of ET-1. These results are consistent with the ET-1 induced inhibition of the evoked release of ATP being due to activation of ETB receptors.
Westfall
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TC
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, MO 63104, USA.
Yang
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Rotto-Perceley
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Macarthur
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D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009451:Neuroeffector Junction / Q000187:drug effects* / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
D009478:Neuropeptide Y; D000255:Adenosine Triphosphate