title: Soluble guanylyl cyclase activators increase the expression of tolerance to morphine analgesic effect.
abstract: OBJECTIVE
  It is aimed to investigate the effects of guanylyl cyclase activation and inhibition on acute morphine antinociception and the development of tolerance to its effect.
  
  
  BACKGROUND
  Nitric oxide-soluble guanylyl cyclase signal transduction cascade suggested to play an important role in the development of tolerance to antinociceptive effects of morphine.
  
  
  METHODS
  Nociception was evaluated by tail flick and hot plate tests in male Wistar rats. The analgesic effects of intraperitoneal protoporphyrin IX (PPIX; an activator of soluble guanylyl cyclase), 3-morpholinosydnonimine hydrochloride (SIN-1; NO donor and activator of guanylyl cyclase), S-Nitroso-N-acetylpenicillamine (SNAP; an activator of guanylyl cyclase), 3,3-Bis (amino ethyl)-1-hydroxy-2-oxo-1-triazene (NOC-18; NO donor activating guanylyl cyclase) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; an inhibitor of guanylyl cyclase) alone or in combination with subcutaneous morphine injection were evaluated. Their effects on morphine tolerance development were evaluated by giving these agents 20 minutes prior to twice daily morphine injection during tolerance development for 5 days. On day 6, the expression of morphine tolerance was determined.
  
  
  RESULTS
  PPIX, SIN-1, SNAP and NOC-18 significantly increased expression of morphine tolerance while ODQ decreased.
  
  
  CONCLUSIONS
  These data suggested that sGC activators have a significant role in tolerance to the analgesic effect of morphine (Tab. 1, Fig. 4, Ref. 29).
authors.forename: N
authors.initials: N
authors.lastname: Durmus
authors.forename: I
authors.initials: I
authors.lastname: Bagcivan
authors.forename: E
authors.initials: E
authors.lastname: Ozdemir
authors.forename: A
authors.initials: A
authors.lastname: Altun
authors.forename: S
authors.initials: S
authors.lastname: Gursoy
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance; D020536:Enzyme Activators / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism*; D015183:Restriction Mapping; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D000071756:Soluble Guanylyl Cyclase
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000701:Analgesics, Opioid; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D010069:Oxadiazoles; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D011810:Quinoxalines; D018160:Receptors, Cytoplasmic and Nuclear; C002385:linsidomine; D009020:Morphine; D026423:S-Nitroso-N-Acetylpenicillamine; C028025:protoporphyrin IX; D008981:Molsidomine; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase