Nitric oxide and prostaglandins in the clenbuterol-induced ACTH and corticosterone secretion.
The present study was designed to determine the involvement of nitric oxide (NO) and prostaglandins (PG) in the stimulatory action of clenbuterol, a selective beta(2)-adrenergic receptor agonist on hypothalamic-pituitary-adrenal (HPA) axis under basal and social crowding stress conditions. Clenbuterol given i.c.v. (10 microg) or i.p. (0.2 mg/kg) considerably increased ACTH and corticosterone secretion. A selective beta(2)-receptor antagonist compound ICI 118551 and non-selective beta-receptor antagonist propranolol given by either route reduced the stimulatory action of clenbuterol. Crowding stress (21 rats in a cage for 7) for 3-7 days significantly reduced the i.c.v. clenbuterol-induced ACTH and corticosterone secretion and i.p. clenbuterol-elicited ACTH secretion. L-NAME, mainly endothelial nitric oxide synthase (NOS) blocker, stronger than L-NNA, a neuronal NOS blocker, reduced the clenbuterol-evoked ACTH and corticosterone secretion in control rats but did not significantly alter this secretion already reduced by crowding stress. Piroxicam, predominantly constitutive cyclooxygenase (COX-1) inhibitor, given i.p. significantly diminished the i.p. clenbuterol-induced ACTH and corticosterone secretion in control rats and tended to reverse the reduction of ACTH secretion by crowding stress. These results indicate that clenbuterol, a selective beta(2)-adrenoceptor agonist, is much stronger stimulator of the HPA axis than isoprenaline, a non-selective beta-receptor agonist. Social crowding stress reduces to a larger extent the HPA response to beta(2)-receptor stimulation. Likewise, in the HPA axis stimulation via beta(2)-adrenoceptors endogenous NO and prostaglandins are significantly involved. Beta2-adrenoceptor is a dominant functional subtype of beta-receptor in the stimulatory and modulatory signals regulating the HPA axis activity under basal and social stress conditions.
Gadek-Michalska
A
A
Department of Physiology, Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland.
Bugajski
A J
AJ
Bugajski
J
J
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000324:Adrenocorticotropic Hormone / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002976:Clenbuterol / Q000008:administration & dosage / Q000494:pharmacology*; D003345:Corticosterone / Q000378:metabolism*; D003441:Crowding / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism; D013315:Stress, Psychological / Q000503:physiopathology
D000318:Adrenergic beta-Agonists; D011453:Prostaglandins; D018343:Receptors, Adrenergic, beta-2; D009569:Nitric Oxide; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D002976:Clenbuterol