Involvement of constitutive (COX-1) and inducible cyclooxygenase (COX-2) in the adrenergic-induced ACTH and corticosterone secretion.

The involvement of prostaglandins synthesized by constitutive (COX-1) and inducible cyclooxygenase (COX-2) in central stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by adrenergic receptor agonists was investigated in conscious rats. COX-1 and COX-2 inhibitor, piroxicam (0.02 and 0.2 microg) and compound NS-398 (0.01 and 0.1 microg), respectively, were given intracerebroventricularly (i.c.v.) 15 min prior to i.c.v. adrenergic receptor agonists: phenylephrine (30 microg) and clonidine (10 microg), an alpha1- and alpha2-adrenergic agonist, and isoprenaline (20 microg) a non-selective beta-adrenergic agonist and clenbuterol (10 microg) a selective beta2-adrenergic agonist. Piroxicam and NS-398 considerably and dose-dependently reduced the phenylephrine-induced increase in ACTH and corticosterone secretion. Pretreatment with piroxicam and NS-398 markedly impaired the clonidine-evoked ACTH and corticosterone secretion. Piroxicam moderately diminished the isoprenaline-elicited increase in ACTH and corticosterone, while NS-398 did not markedly alter ACTH secretion. The clenbuterol-induced ACTH and corticosterone responses were considerably impaired by pretreatment with piroxicam, and slightly less potently by NS-398. These results indicate that in central structures involved in regulation of the HPA axis both constitutive and inducible cyclooxygenase are present under normal conditions in rats. These isoenzymes are significantly involved in the stimulatory signaling transduced by postsynaptic alpha1-adrenergic receptors and, to a lesser extent, by alpha2-adrenergic receptors. Both isoenzymes affect moderately the stimulatory action of a non-selective beta-adrenergic agonist on ACTH and corticosterone secretion. COX-1 participates considerably and COX-2 markedly in the potent stimulatory action of selective beta2-adrenergic receptors on HPA axis.