title: Bradykinin B2 receptor in the adrenal medulla of male rats and mice: glucocorticoid-dependent increase with immobilization stress.
abstract: Bradykinin, acting via the bradykinin B2 receptor (B2R), is a potent stimulator of adrenomedullary catecholamine biosynthesis and release and likely plays an important role in the adrenomedullary stress response. However, the effects of stress on the expression of this receptor in the adrenal medulla are currently unclear. Here, we examined the changes in adrenomedullary B2R gene expression in male rats in response to single (1 time) and repeated (6 times) exposure to 2 hours immobilization stress (IMO). Immediately after 1 or 6 times IMO, B2R mRNA levels were increased by 9-fold and 7-fold, respectively, and returned to unstressed control levels 3 hours later. This large, but transient, increase in mRNA elicited a doubling of protein levels 3 hours after the stress exposure. Next, the role of the hypothalamic-pituitary-adrenocortical axis in the stress-induced upregulation of B2R gene expression was examined. Treatment with endogenous (corticosterone) and synthetic (dexamethasone) glucocorticoids dose-dependently increased B2R mRNA levels in adrenomedullary-derived PC12 cells. Furthermore, cortisol supplementation at levels mimicking stress exposure elevated B2R mRNA levels in the adrenal medulla of hypophysectomized rats. In response to 1 exposure to IMO, the stress-triggered rise in plasma corticosterone and adrenomedullary B2R mRNA levels was attenuated in CRH-knockout mice and absent in pharmacologically adrenalectomized rats, indicating a requirement for glucocorticoids in the upregulation of B2R gene expression with stress. Overall, the increase in B2R gene expression in response to the stress-triggered rise in glucocorticoids likely enhances catecholamine biosynthesis and release and may serve as an adaptive response of the adrenomedullary catecholaminergic system to stress.
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595. esther_sabban@nymc.edu.
authors.forename: Regina
authors.initials: R
authors.lastname: Nostramo
authors.forename: Andrej
authors.initials: A
authors.lastname: Tillinger
authors.forename: Lidia
authors.initials: L
authors.lastname: Serova
authors.forename: Richard
authors.initials: R
authors.lastname: Kvetnansky
authors.forename: Esther L
authors.initials: EL
authors.lastname: Sabban
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D006854:Hydrocortisone / Q000008:administration & dosage / Q000378:metabolism; D007016:Hypophysectomy; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016716:PC12 Cells; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012149:Restraint, Physical; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D043782:Receptor, Bradykinin B2; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone; D006854:Hydrocortisone