title: Differential effects of two kappa-opiate agonists, U-50,488H and U-69,593, on the binding of 3H-(3-MeHis2) thyrotropin-releasing hormone to rat spinal cord and amygdala membranes.
abstract: The effect of delta- and kappa-opiate receptor agonists on the binding of 3H-(3-MeHis2) thyrotropin-releasing hormone (3H-MeTRH) to membranes of the spinal cord and amygdala of male Sprague-Dawley rats was determined in an effort to further understand interactions between opiates and TRH receptors. The agonists used were D-Ala2-MePhe4-Gly-ol5-enkephalin (DAMGO, mu-receptor), cyclic D-penicillamine2-D-penicillamine5-enkephalin (DPDPE, delta-receptor), cyclic D-penicillamine2-L-penicillamine5-enkephalin (DPLPE, delta-receptor), D-Ala2-D-Leu5-enkephalin (delta-receptor), U-50,488H and U-69,593 (kappa-receptor). 3H-MeTRH bound to amygdala and spinal cord membranes at a single site with Bmax values of 35.7 +/- 5.4 and 15.8 +/- 2.6 fmol/mg protein, and Kd values of 6.3 +/- 1.1 and 5.2 +/- 0.7 nmol/l, respectively. The competition experiments were carried out at a concentration of 2 nmol/l 3H-MeTRH. The concentration of opiate ranged from 10(-9) to 10(-4) mol/l. DAMGO, DPDPE and DPLPE had no effect on the binding of 3H-MeTRH to amygdala or spinal cord membranes. The two highly selective kappa-agonists differed in their interaction with TRH receptors. Whereas U-69,593 did not modify the binding of 3H-MeTRH, U-50,488H significantly inhibited the binding of 3H-MeTRH to both spinal cord and amygdala membranes. U-50,488H has been found to be 10 times more potent than U-69,593 at the central kappa-opiate receptors and may explain their differential action at the TRH receptors. It is concluded that mu- and delta-opiate agonists do not interact with brain and spinal cord TRH receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacodynamics (m/c 865), University of Illinois, Chicago.
authors.forename: N H
authors.initials: NH
authors.lastname: Rahmani
authors.forename: A
authors.initials: A
authors.lastname: Gulati
authors.forename: H N
authors.initials: HN
authors.lastname: Bhargava
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D001667:Binding, Competitive / Q000187:drug effects; D004745:Enkephalins / Q000494:pharmacology; D008297:Male; D008566:Membranes; D011759:Pyrrolidines / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D017473:Receptors, Opioid, kappa; D018025:Receptors, Thyrotropin-Releasing Hormone; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000700:Analgesics; D044482:Benzeneacetamides; D004745:Enkephalins; D011759:Pyrrolidines; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D018025:Receptors, Thyrotropin-Releasing Hormone; C014109:thyrotropin-releasing hormone, 3-Me-; D013973:Thyrotropin-Releasing Hormone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C045444:U 69593; D011761:Pyrrolidonecarboxylic Acid