title: Micromolar substance P reduces spinal receptor binding for thyrotropin-releasing hormone--possible relevance to neuropeptide coexistence?
abstract: Receptors for thyrotropin-releasing hormone (TRH) on membranes of rat spinal cord (SC) were labeled with [3H](3-Me-His2)TRH ([3H]MeTRH) (dissociation constant = 3.6 +/- 0.8 (6) nM). Substance P (SP) caused a concentration-dependent inhibition of TRH receptor binding in the micromolar range (43 +/- 4 (6)% at 50 microM). Scatchard analyses of competition data revealed that 50 microM SP reduced TRH receptor number (40-66%, P less than 0.05) with little or no effect on affinity. SP appeared more potent in reducing [3H]MeTRH binding to ventral cord membranes than those of dorsal or whole SC. A number of SP analogs also reduced TRH receptor binding in a dose-related manner but with different potencies. In contrast, various amino acids and serotonin (250 microM) produced little or no inhibition of [3H]MeTRH binding, and cholecystokinin, Leu- and Met-enkephalins, angiotensin II, LH-RH, bombesin and somatostatin were also markedly less potent than SP. Although it is unclear whether spinal TRH receptors are ever exposed to micromolar concentrations of SP in vivo, the reported colocalization of these neuropeptides in raphe efferents to the SC suggests that our findings may be of physiological relevance.
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004525:Efferent Pathways / Q000187:drug effects / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011869:Radioligand Assay; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D018025:Receptors, Thyrotropin-Releasing Hormone; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000378:metabolism*
chemical_list: D011956:Receptors, Cell Surface; D018025:Receptors, Thyrotropin-Releasing Hormone; D013373:Substance P; C014109:thyrotropin-releasing hormone, 3-Me-; D013973:Thyrotropin-Releasing Hormone; D011761:Pyrrolidonecarboxylic Acid