Effect of thyrotropin releasing hormone on U-50,488H-induced pharmacological responses in mice.
The effect of thyrotropin releasing hormone (TRH) administered either subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) on the analgesic and hypothermic actions of U-50,488H, a highly selective kappa-opiate agonist, was determined in male Swiss Webster mice. Intraperitoneal administration of U-50,488H (8-32 mg/kg) produced a dose-dependent analgesia as assessed by the tail-flick test. Similarly, U-50,488H also produced a dose-dependent hypothermia in mice. TRH was administered s.c. 15 min or i.c.v. 5 min prior to U-50,488H injection. TRH (1,3 and 10 mg/kg, s.c.) dose-dependently attenuated the analgesic effect of U-50,488H (32 mg/kg), whereas TRH at these doses displayed almost complete blockade of the hypothermic effect of U-50,488H. Similarly, TRH (0.03, 0.3 and 1 microgram/mouse; i.c.v.) dose-dependently attenuated the analgesic and hypothermic actions of U-50,488H, indicating the central component in the action of TRH. TRH alone in doses used showed no change in either basal tail-flick latency or body temperature, demonstrating the lack of effect of this drug alone on pain and temperature responsiveness. Studies have shown that TRH does not modify morphine or beta-endorphin-induced analgesia in animals nor does it affect the binding of mu-opiate agonist or antagonist to brain membranes. Previous studies from this laboratory have indicated that kappa-opiates but not mu-opiates inhibit the binding of [3H][3-MeHis2]-TRH to brain membranes. The present studies clearly show that TRH modulates the pharmacological actions mediated by kappa-opiate agonists in mice. Thus, these studies provide further in vivo evidence for an acute interaction between TRH and kappa-opiates.
Bhargava
H N
HN
Department of Pharmacodynamics (M/C 865), University of Illinois at Chicago, Health Sciences Center 60612.
Thorat
S N
SN
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D003106:Colon; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011759:Pyrrolidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D000700:Analgesics; D011759:Pyrrolidines; D013973:Thyrotropin-Releasing Hormone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer