title: Hypothalamic atrial natriuretic peptide secretion plasticity: differential modulation of alpha and beta adrenoceptors.
abstract: Increasing evidence suggests that atrial natriuretic peptide (ANP), a 28 amino acid peptide with biologically active 4-28 and 5-28 congeners, modulates salt-water homeostasis at both peripheral and central levels. In rats, immunoreactive (ir) ANP is found in hypothalamic (HT) neurons of preoptic and paraventricular regions rich in aminergic innervation. Employing a well-characterized perifusion model of rat HT explants, the acute effects of norepinephrine (NE) on HT release of irANP were examined. Pulsatile administration (20 min) of NE (10(-7) to 10(-5) M) induced a dose-related release of irANP. The stimulatory effect of 10(-5) M NE (2.66 +/- 0.54 pg/ml/HT, means +/- SE, n = 12) was abolished in the presence of 10(-7) M propranolol, a beta-antagonist, but was 50% higher when administrated with 10(-5) M phentolamine, an alpha-antagonist. Administration of equivalent doses of propranolol or phentolamine alone, consistently suppressed (40% below basal secretion rate, BSR) or stimulated (50% above BSR) irANP release, respectively. In addition, infusion of isoprenaline (10(-5) M), a beta-agonist, enhanced BSR by 45%, whilst phenylephrine (10(-5) M), an alpha-agonist, suppressed it by 25%. We conclude that in rat hypothalami (1) occupancy of the beta-adrenoceptor by its agonist stimulates irANP release, (2) alpha- and beta-adrenoceptors modulate irANP secretion in an opposing manner, and (3) the basal release of irANP is a product of the activation of alpha- and beta-adrenoceptors by their endogenous ligands.
authors.affiliation: Mental Health Research Institute of Victoria, Royal Park Hospital, Parkville, Australia.
authors.forename: A I
authors.initials: AI
authors.lastname: Bush
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.forename: D L
authors.initials: DL
authors.lastname: Copolov
authors.forename: A T
authors.initials: AT
authors.lastname: Lim
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
chemical_list: D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D011433:Propranolol; D007545:Isoproterenol; D009638:Norepinephrine; D010646:Phentolamine