title: Evidence for opiate action at the brain receptors for thyrotropin-releasing hormone.
abstract: The effect of drugs acting on mu-, delta-, kappa- and sigma-opiate receptors on the binding of [3H-3-MeHis2]thyrotropin releasing hormone ([3H-Me]TRH) to rat brain membranes was determined. The drugs used included morphine and naloxone (mu-ligands), N,N-bisallyl-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH (ICI 154, 129, delta-ligand), ethylketocyclazocine (EKC, kappa-ligand), and N-allylnormetazocine (SKF-10,047, sigma-ligand). [3H-Me]TRH bound specifically to brain membranes at a single high-affinity site with a Bmax value of 50 fmol/mg protein and a Kd of 5 nM. A concentration of 2 nM of [3H-Me]TRH was used for in vitro interaction studies. The binding of [3H-Me]-TRH was unaffected by morphine or naloxone up to and including 1 mM concentration, but was inhibited by ICI 154,129 (IC50, 8 X 10(-5) M), EKC (IC50, 3 X 10(-4) M), SKF 10,047 (IC50, 1 mM), and TRH (IC50, 2 X 10(-7) M). In the presence of an IC25 concentration of IDI 154, 129 or EKC, there was a 25% decrease in the Bmax values of [3H-Me]TRH but the apparent dissociation constant, Kd value did not change. The results demonstrate for the first time that ligands acting at the delta- and kappa-opiate receptors interact with the brain TRH receptors; sigma-receptor ligands have weak interaction and mu-receptor ligands do not interact with brain TRH receptors. These results may help in explaining the observed pharmacological interactions between opiates and TRH.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D011956:Receptors, Cell Surface; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone