title: Role of hypothalamic paraventricular nucleus alpha- and beta-adrenergic receptors in regulation of blood glucose, free fatty acids and corticosterone.
abstract: The potential roles of adrenergic and noradrenergic terminals in the hypothalamic paraventricular nucleus in the regulation of blood glucose and free fatty acids, the two major metabolic fuels, were examined. Corticosterone was also measured, both to assess the specificity of any effects for metabolic fuels, and because endogenous catecholamines in this site have previously been implicated in corticosterone regulation. In the first experiment adult male albino rats having chronically implanted guide cannulae aimed at the hypothalamic paraventricular nucleus or the caudate nucleus received microinjections of the agonists methoxamine (alpha 1), clonidine (alpha 2), and isoproterenol (beta) (0, 10, 30, 100 nmol/500 nl), and blood samples were taken from the tail tip. In the second experiment a different set of rats received 30 nmol clonidine or vehicle subcutaneously instead of brain microinjections. Intracranial clonidine and isoproterenol produced marked and moderate hyperglycemia, respectively; methoxamine did not alter glucose. For neither clonidine nor isoproterenol was there any difference in hyperglycemia as a function of microinjection site; also, subcutaneous clonidine injections produced the same peak glucose response as was found after both paraventricular and caudate nucleus microinjections of the same dose. Free fatty acid levels were increased by clonidine and isoproterenol, but slightly suppressed by methoxamine; the alpha agonist effects, but not the beta agonist effect, were greater after paraventricular microinjections than after caudate microinjections. Corticosterone was increased by both alpha agonists after paraventricular but not after caudate nucleus microinjections; beta agonist microinjections into the paraventricular and caudate nuclei produced equivalent corticosterone elevations. These results suggest that most, if not all, of the hyperglycemic effects of alpha and beta adrenergic agonist microinjection into the paraventricular nucleus can be ascribed to leakage of the material into the vasculature, with subsequent action at a distant site. In contrast, all 3 agonists seem capable of acting within the brain to alter free fatty acid levels. The effects on corticosterone of both the alpha 1 and alpha 2 agonists, but not the beta agonist, also appear due, at least in part, to actions within the brain. Previous suggestions that catecholamine terminals in the hypothalamic paraventricular nucleus are directly and strongly involved in metabolic fuel regulation may require reconsideration.
authors.affiliation: Research Service, Sepulveda Veterans Affairs Medical Center, CA 91343.
authors.forename: M W
authors.initials: MW
authors.lastname: Gunion
authors.forename: M J
authors.initials: MJ
authors.lastname: Rosenthal
authors.forename: S
authors.initials: S
authors.lastname: Miller
authors.forename: M A
authors.initials: MA
authors.lastname: Hoyt
authors.forename: D B
authors.initials: DB
authors.lastname: Yonzon
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D007279:Injections, Subcutaneous; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D008845:Microinjections; D010286:Paraventricular Hypothalamic Nucleus / Q000033:anatomy & histology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002395:Catecholamines; D005230:Fatty Acids, Nonesterified; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D008729:Methoxamine; D007545:Isoproterenol; D003000:Clonidine; D003345:Corticosterone