Presynaptic A2-adrenoceptors and neuropeptide Y Y2 receptors inhibit [3H]noradrenaline release from rat hypothalamic synaptosomes via different mechanisms.
Presynaptic receptors may reduce transmitter release with different mechanisms. Both the alpha 2-agonist, clonidine and the Y2-agonist, neuropeptide Y fragment 13-36 (NPY 13-36), induce a concentration-dependent inhibition of the 4-aminopyridine (4-AP)-evoked [3H]noradrenaline ([3H]NA) release from hypothalamic synaptosomes. Changes in alpha 2- and Y2-modulation of noradrenaline (NA) release were observed by lowering the calcium influx with the use of omega-conotoxin (omega-CgTx), a calcium-channel blocking agent. In these experimental conditions, clonidine was less active, whereas NPY 13-36 preserved its efficacy. It therefore seems possible that presynaptic alpha 2-adrenoceptors can primarily inhibit NA release by reducing calcium influx via voltage-sensitive calcium channels (VSCC), while Y2-receptors may inhibit the intracellular release process with a mechanism independent of the calcium entry.
Martire
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Institute of Pharmacology, Catholic University of Sacred Heart, Rome, Italy.
Pistritto
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Mores
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Agnati
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Fuxe
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D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology; D009478:Neuropeptide Y / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D008978:Mollusk Venoms; D009478:Neuropeptide Y; D010446:Peptide Fragments; D010455:Peptides; D018341:Receptors, Adrenergic, alpha-2; D017476:Receptors, Neuropeptide Y; C062924:neuropeptide Y (13-36); D020866:omega-Conotoxin GVIA; D015761:4-Aminopyridine; D003000:Clonidine; D009638:Norepinephrine