Central neurokinin 3 receptors increase systemic oxytocin release: interaction with norepinephrine.
Stimulation of central tachykinin receptors contributes to neuroendocrine functions of the hypothalamo-neurohypophyseal system. However, the specific role of each tachykinin receptor subtype has not been completely characterized. Specifically, while neurokinin 3 (NK3) receptor stimulation increases systemic vasopressin, the effects on oxytocin (OT) are not known. Therefore, the present studies investigated the effect of central NK3 receptor stimulation with senktide on release of systemic and central OT. Furthermore, since central NK3 receptors activate noradrenergic systems, which contribute to OT release, the effects of alpha-adrenergic receptor blockade on senktide-induced changes in OT release were evaluated. Female rats were implanted with a cannula in the third cerebral ventricle, and changes in plasma OT concentration determined before and following central administration of senktide in vehicle-treated rats, and animals following central administration of the alpha-adrenergic antagonist phentolamine. Other rats were implanted with microdialysis probes adjacent to the paraventricular nucleus (PVN), and dialysate and plasma OT concentrations were determined before and during administration of senktide through the dialysis probe. Central senktide increased systemic OT release, which was prevented by pretreatment with phentolamine. Furthermore, there was no detectable change in extracellular OT concentration in the PVN during dialysis administration of senktide. These data demonstrate that activation of central NK3 receptors stimulates systemic release of OT by activation of central noradrenergic systems, apparently without increasing intranuclear OT release in the PVN.
Bealer
Steven L
SL
Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT 84112-5820, USA. steve.bealer@deans.pharm.utah.edu
Flynn
Francis W
FW
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007276:Injections, Intraventricular; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism*; D010121:Oxytocin / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018042:Receptors, Neurokinin-3 / Q000378:metabolism*; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D010446:Peptide Fragments; D018042:Receptors, Neurokinin-3; C054724:senktide; D013373:Substance P; D010121:Oxytocin; D009638:Norepinephrine; D010646:Phentolamine