Substance P and NPY differentially potentiate ATP and adrenergic stimulated vasopressin and oxytocin release

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2001-01, Vol.280 (1), p.69-R78
• Main Authors: Kapoor, John R, Sladek, Celia D
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Adrenergic alpha-Agonists - pharmacology; Animals; Cells, Cultured; Drug Synergism; Hypothalamo-Hypophyseal System - metabolism; Male; Neuropeptide Y - analogs & derivatives; Neuropeptide Y - pharmacology; Norepinephrine - metabolism; Oxytocin - metabolism; Phenylephrine - pharmacology; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Signal Transduction - physiology; Substance P - pharmacology; Supraoptic Nucleus - cytology; Supraoptic Nucleus - drug effects; Supraoptic Nucleus - metabolism; Vasopressins - metabolism
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.2001.280.1.r69

Department of Physiology and Biophysics, Finch University of Health Sciences/ The Chicago Medical School, North Chicago, Illinois 60064 The supraoptic nuclei are innervated by the A1 neurons of the caudal ventrolateral medulla. Substances colocalized in the A1 terminals include norepinephrine (NE), substance P (SP), ATP, and neuropeptide Y (NPY). ATP, acting at P 2x receptors, caused rapid and unsustained stimulation of vasopressin (VP) and oxytocin (OT) release from perifused explants of the hypothalamo-neurohypophysial system. SP elicited a concentration-dependent stimulation of VP and OT release that was large and sustained compared with other stimuli. ATP, but not phenylephrine (PE, 1 -adrenergic agonist), augmented the response to SP (1 µM). In contrast, NPY did not alter basal nor ATP-induced VP or OT release, but it did cause sustained potentiation of PE-induced VP and OT release. The Y 1 -agonist, [Leu 31 ,Pro 34 ]-NPY, increased VP and OT release, suggesting that the ineffectiveness of NPY reflects opposing actions at pre- and postsynaptic receptors. However, [Leu 31 ,Pro 34 ]-NPY did not potentiate hormone responses to ATP or PE. The differential responses to these colocalized neurotransmitters and neuropeptides illustrate the range of potential responses that stimulation of this pathway might elicit from supraoptic neurons. norepinephrine; A1 neurons; neurohypophysis; supraoptic nucleus; hemodynamic regulation