Analogs of thyrotropin-releasing hormone (TRH): receptor affinities in brains, spinal cords, and pituitaries of different species.
[3H](3-Me-His2) thyrotropin-releasing hormone ([3H]MeTRH) bound to TRH receptors in rodent, rabbit and dog brain and spinal cord (SC), and in rat, sheep, bovine and dog anterior pituitary (PIT) glands, with high affinity (dissociation constants, KdS = 5-9 nM; n = 3-4) but to different densities of these sites (Bmax range 6-145 fmol/mg protein) (rabbit SC greater than sheep PIT much greater than G.pig brain greater than dog brain greater than rat brain greater than bovine and dog PIT). Various TRH analogs competitively inhibited [3H]MeTRH binding in these tissues with a similar rank order of potency: MeTRH greater than TRH greater than CG3703 greater than or equal to RX77368 greater than or equal to MK-771 greater than TRH Glycinamide greater than Glu1-TRH much greater than CG3509 greater than or equal to NVal2-TRH much much greater than TRH free acid much much greater than and cyclo-His-Pro, indicating a pharmacological similarity of CNS and pituitary TRH receptors. While most TRH analogs displaced [3H]MeTRH binding with a similar potency in the different species, TRH exhibited a 2-fold lower affinity in the rat and G.pig brain than in other tissues of other species. Similarly, CG3703 was 2.4-4.5 times more active in the rabbit brain than in the rodent and dog brain, and also more potent in the rabbit brain as compared to the sheep PIT.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Neuroscience, Institute of Pharmacology Syntex Research, Palo Alto, CA 94303.
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D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D004285:Dogs; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011817:Rabbits; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D018025:Receptors, Thyrotropin-Releasing Hormone; D012756:Sheep; D013045:Species Specificity; D013116:Spinal Cord / Q000378:metabolism*; D053778:Thiazolidines; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism
D017981:Receptors, Neurotransmitter; D018025:Receptors, Thyrotropin-Releasing Hormone; D053778:Thiazolidines; C031926:montirelin; C014109:thyrotropin-releasing hormone, 3-Me-; D013973:Thyrotropin-Releasing Hormone; C021597:pyro(l-alpha-aminoadipyl)-L-histidyl-L-thiazolidine-4-carboxamide; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D011761:Pyrrolidonecarboxylic Acid