ABSTRACT
Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3′,5′-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress.
Subject(s)
Animals , Male , Acute Pain/prevention & control , Carbon Monoxide/metabolism , Cyclic GMP/metabolism , Heme Oxygenase (Decyclizing)/metabolism , Nociceptive Pain/prevention & control , Stress Disorders, Traumatic, Acute/metabolism , Cyclic GMP/antagonists & inhibitors , Deuteroporphyrins/metabolism , Heme Oxygenase (Decyclizing)/antagonists & inhibitors , Heme/analogs & derivatives , Heme/metabolism , Lysine/analogs & derivatives , Lysine/metabolism , Nociceptive Pain/metabolism , Oxadiazoles/pharmacology , Pain Measurement/methods , Rats, Wistar , Signal Transduction/physiologyABSTRACT
Leptospira interrogans serovar canicola strain moulton was grown to a high cell density in a protein-free medium. When hemin was added to this medium, hemolysin was produced. Hemolysin was not detected when other porphyrins or cytochrome C were substituted for hemin in the medium.