RT Journal Article
SR Electronic
T1 Endomorphin-1 and Endomorphin-2 Show Differences in Their Activation of μ Opioid Receptor-Regulated G Proteins in Supraspinal Antinociception in Mice
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 12
OP 18
VO 291
IS 1
A1 Pilar Sánchez-Blázquez
A1 Marta Rodríguez-Díaz
A1 Isabel DeAntonio
A1 Javier Garzón
YR 1999
UL http://jpet.aspetjournals.org/content/291/1/12.abstract
AB Endomorphin-1 and endomorphin-2 are tetrapeptides of the brain whose binding profiles and analgesic activities indicate that they are endogenous ligands at μ opioid receptors. To analyze the classes of G transducer proteins activated by these opioids in the production of supraspinal antinociception, the expression of α subunits of the Gi protein class, Gi1, Gi2, Gi3, Go1, Go2, and Gz, and those of the Gq protein family, Gq and G11, was reduced by administration of antisense oligodeoxynucleotides (ODNs) complementary to sequences in their respective mRNAs. The ODN treatments promoted differences in the analgesic effects displayed by morphine, [d-Ala2,N-MePhe4,Gly-ol5]enkephalin (DAMGO), and the novel opioids endomorphin-1 and endomorphin-2. The impairment of Gi1α and Gi3α function led to a weaker analgesic response to the endomorphins and to the α2-adrenoceptor agonist clonidine, whereas the effects of morphine and DAMGO were not affected. An antisense probe targeting Gi2α blocked the antinociceptive effects of endomorphin-2, morphine, DAMGO, and clonidine but was without effect on the activity of endomorphin-1. Mice receiving the ODN to Gzα subunits showed impaired response to all agonists. The knockdown of either Go1α, Go2α, Gqα, or G11α had little or no influence on the antinociception induced by any of the opioids in the study. Thus, agonists exhibit differences in activating the variety of GTP-binding proteins regulated by μ opioid receptors. The American Society for Pharmacology and Experimental Therapeutics