title: Neuronostatin acts in brain to biphasically increase mean arterial pressure through sympatho-activation followed by vasopressin secretion: the role of melanocortin receptors.
abstract: Neuronostatin is a recently described neuropeptide that is derived from the somatostatin preprohormone. We have shown previously that neuronostatin led to a biphasic, dose-related increase in mean arterial pressure when injected into the lateral cerebroventricle of adult, male rats. Because neuronostatin depolarized both magnocellular and parvocellular, paraventricular nucleus neurons in hypothalamic slice preparations, we hypothesized that neuronostatin elevated mean arterial pressure first by stimulating sympathetic nervous system activity followed by the release of a pressor hormone, specifically vasopressin. We found that the first phase of neuronostatin-induced increase in mean arterial pressure was reversed by pretreatment with phentolamine, indicating that phase 1 was, indeed, due to an increase in sympathetic activity. We also found that centrally injected neuronostatin led to a dose-related increase in vasopressin secretion in a time course consistent with the peak of the second phase. Furthermore, the second phase of arterial pressure elevation was reversed by pretreatment with a vasopressin 1 receptor antagonist, indicating that phase 2 was likely due to an increase in vasopressin secretion. We previously have shown that the anorexigenic and antidipsogenic effects of neuronostatin were reversed by pretreatment with the melanocortin 3/4 receptor antagonist, SHU9119, so we evaluated the ability of SHU9119 to reverse the effects of neuronostatin on MAP and vasopressin secretion. We found that SHU9119 abrogated the second phase of neuronostatin-induced increase in MAP and neuronostatin-induced vasopressin secretion, indicating that neuronostatin acts through the central melanocortin system to increase vasopressin release, ultimately leading to an elevation in MAP.
authors.affiliation: Dept. of Pharmacological and Physiological Science, Saint Louis University, St Louis, MO 63104, USA. gyosten@slu.edu
authors.forename: Gina L C
authors.initials: GL
authors.lastname: Yosten
authors.forename: Alicia T
authors.initials: AT
authors.lastname: Pate
authors.forename: Willis K
authors.initials: WK
authors.lastname: Samson
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006727:Hormone Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D044101:Receptors, Melanocortin / Q000187:drug effects* / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000378:metabolism; D013004:Somatostatin / Q000008:administration & dosage* / Q000031:analogs & derivatives; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013997:Time Factors; D014667:Vasopressins / Q000378:metabolism*
chemical_list: D000317:Adrenergic alpha-Antagonists; D006727:Hormone Antagonists; D010446:Peptide Fragments; D044101:Receptors, Melanocortin; D017483:Receptors, Vasopressin; D014667:Vasopressins; C103272:SHU 9119; D013004:Somatostatin; D009074:Melanocyte-Stimulating Hormones; D010646:Phentolamine