Simultaneous modulation of TRH and opioid receptor binding in rat spinal cord after chronic naloxone administration.
[3H]MeTRH binds to crude membranes prepared from the spinal cord with high affinity, K = 3.13 (+/- 0.29) x 10(8) L/M. After chronic treatment with naloxone (2 mg-kg/h), the density of spinal opioid (mu) receptors increased 100% at the same time as the following changes in MeTRH binding were observed: the affinity of [3H]MeTRH decreased 58% (K = 1.32 (+/- 0.17) x 10(8) L/M; p less than 0.005), and binding capacity increased 71%, from 28 (+/- 4) x 10(-12) M/L or 56 fmol/mg protein to 48 (+/- 9) x 10(-12) M/L or 96 fmol/mg (p less than 0.05). The relative potencies of TRH and MeTRH in competition for the binding of [3H]MeTRH changed from a high IC50 ratio of 10 in control rats to a low IC50 ratio of about 3 only after naloxone treatment. The results of this study show for the first time that the opiate antagonist-induced upregulation of opioid receptors is associated with modulation in binding of TRH receptors.
Krumins
S A
SA
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D018025:Receptors, Thyrotropin-Releasing Hormone; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000493:pharmacokinetics*
D004745:Enkephalins; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D018025:Receptors, Thyrotropin-Releasing Hormone; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D013973:Thyrotropin-Releasing Hormone