Role of nitric oxide/cyclic GMP in i.c.v. administered beta-endorphin- and (+)-cis-dioxolane-induced antinociception in the mouse.
(+)-cis-Dioxolane (0.5-2 micrograms), a muscarinic receptor agonist, given intracerebroventricularly (i.c.v.) produced a dose-dependent inhibition of the tail-flick response in male ICR mice. (+)-cis-Dioxolane given i.c.v. at a subanalgesic dose (0.25 micrograms), selectively potentiated the antinociceptive response induced by i.c.v. administered beta-endorphin, an epsilon-opioid receptor agonist, but not morphine or [D-Ala2,NMePhe4,Gly5-ol]enkephalin (DAMGO), mu-opioid receptor agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE), a delta receptor agonist, or trans(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methane sulfonate (U50,488H), a kappa-opioid receptor agonist. The antinociceptive response induced by (+)-cis-dioxolane given i.c.v. was attenuated by i.c.v. treatment with N omega-nitro-L-arginine (1 microgram), hemoglobin (120 micrograms) or methylene blue (10 micrograms). The antinociception induced by carbachol given i.c.v. was also antagonized by the i.c.v. treatment with N omega-nitro-L-arginine (1 microgram). However, the same treatment with N omega-nitro-L-arginine, hemoglobin or methylene blue did not affect the beta-endorphin-induced antinociception. The potentiation of beta-endorphin-induced antinociception by (+)-cis-dioxolane was reversed by i.c.v. treatment with N omega-nitro-L-arginine (1 microgram), hemoglobin (120 micrograms) or methylene blue (10 micrograms). On the other hand, the antinociceptive response induced by (+)-cis-dioxolane (1 microgram) given i.c.v. was potentiated by i.c.v. administered L-arginine (20 micrograms) but not D-arginine (20 micrograms). Dibutyryl cyclic GMP at 0.5-2.0 micrograms given i.c.v. produced an antinociceptive response and at subanalgesic dose (0.1 microgram) potentiated i.c.v. beta-endorphin-induced antinociception.(ABSTRACT TRUNCATED AT 250 WORDS)
Xu
J Y
JY
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
Tseng
L F
LF
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000698:Analgesia; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D004148:Dioxolanes / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000819:agonists; D013237:Stereoisomerism; D001615:beta-Endorphin / Q000008:administration & dosage / Q000494:pharmacology*
D000700:Analgesics; D004148:Dioxolanes; D004745:Enkephalins; D006454:Hemoglobins; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D019335:Nitroarginine; D009569:Nitric Oxide; D001615:beta-Endorphin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D001120:Arginine; D006152:Cyclic GMP; D008751:Methylene Blue