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

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