title: Pretreatment with pertussis toxin differentially modulates morphine- and beta-endorphin-induced antinociception in the mouse.
abstract: The experiments were designed to determine the role of pertussis toxin-(PTX) sensitive G-proteins Gi/Go in the brain and spinal cord in antinociception induced by epsilon-opioid receptor agonist beta-endorphin (beta-EP) and mu-opioid receptor agonist morphine. The effects of intracerebroventricular (i.c.v.) or intrathecal (i.t.) pretreatment with PTX on antinociception induced by morphine, beta-endorphin (beta-EP) and other selective opioid receptor agonists given i.c.v. or i.t. were studied in male ICR mice. Antinociception was assessed by the tail-flick and hot-plate tests. An i.c.v. pretreatment with PTX (0.5 microgram) caused a time- and dose-dependent attenuation of the tail-flick and hot-plate inhibition induced by i.c.v.-challenged morphine-induced antinociception. However, the same pretreatment with PTX did not affect the antinociception induced by i.c.v.-administered beta-EP. The tail-flick and hot-plate inhibition induced by selective mu-, delta- and kappa-opioid receptor agonist, DAMGO, [D-Ala2]deltorphin II and U50,488H, respectively, given i.c.v. was also attenuated by the i.c.v. pretreatment with PTX. An i.t. pretreatment with PTX (0.5 microgram) blocked markedly the tail-flick inhibition induced by morphine and beta-EP given i.c.v. However, the same treatment did not affect the hot-plate inhibition induced by beta-EP and attenuated, to a lesser degree, the hot-plate inhibition induced by morphine given i.c.v. An i.t. pretreatment with PTX blocked the tail-flick inhibition induced by selective delta 2-, alpha 2 and 5-HT receptor agonist [D-Ala2]deltorphin, norepinephrine and 5-HT, respectively, given i.t. Our results indicate that the antinociception induced by mu-, delta-, kappa-opioid receptor agonists given supraspinally is mediated by respectively opioid receptors that are coupled to PTX-sensitive Gi/Go proteins at the supraspinal sites and subsequently mediated by the activation of PTX-sensitive Gi/Go coupled receptors in the spinal cord. However, the antinociception induced by beta-EP given supraspinally is mediated by the PTX-resistant epsilon-opioid receptors at the supraspinal sites and subsequently activation of the delta 2-opioid receptors in the spinal cord that is sensitive to the pretreatment with PTX.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, USA.
authors.forename: L F
authors.initials: LF
authors.lastname: Tseng
authors.forename: K A
authors.initials: KA
authors.lastname: Collins
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000698:Analgesia; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D037342:Pertussis Toxin; D011759:Pyrrolidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*; D001615:beta-Endorphin / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D004745:Enkephalins; D011759:Pyrrolidines; D011985:Receptors, Serotonin; D010566:Virulence Factors, Bordetella; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D001615:beta-Endorphin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins