Pharmacological characterization of opioid receptors influencing the secretion of corticotrophin releasing factor in the rat.

The effects of selective agonists and antagonists of opioid receptors on the secretion of corticotrophin releasing factor (CRF) by isolated rat hypothalami in vitro were studied. Morphine (10(-8)-10(-6) M) and the mu-opioid receptor agonists, FK33-824CH (10(-8)-10(-6) M) and Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH (10(-8)-10(-6) M), caused dose-related increases in the release of CRF from isolated hypothalami. The kappa-opioid receptor agonist, U50,488 (10(-8)-10(-6) M), was also weakly active in this respect but the delta-opioid receptor agonist, (D-Pen2,D-Pen5)-enkephalin (2 X 10(-10)-2 X 10(-7) M), was not. The stimulatory actions of morphine and Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH on CRF release were antagonized by naloxone (10(-8) M) and by the mu/delta-opioid receptor antagonist, beta-funaltrexamine (beta-FNA, 10(-9) M), but not by the delta-opioid receptor antagonist, ICI-154129 (5 X 10(-6) M). The effects of U50,488 on CRF release were unaffected by either beta-FNA or ICI-154129 but were antagonized by high doses of naloxone (10(-6) M). The results suggest that both mu- and kappa-opioid receptors are involved in the stimulation of CRF secretion but that delta-opioid receptors are not important in this respect.