Evidence for a role of nitric oxide in the corticotropin-releasing factor release induced by interleukin-1 beta.
Interleukin-1 beta stimulates corticotropin-releasing factor (CRF) secretion from the hypothalamus involving the activation of prostaglandins. This study investigated the possibility that nitric oxide (NO) acts as a mediator of interleukin-1-induced CRF release. An in vitro rat hypothalami continuous perifusion system was used. Pre- and co-incubation of hypothalami with either the NO synthase inhibitor, NG-nitro-L-arginine (1 mM), or the NO scavenger, hemoglobin (10 microM), induced a marked reduction in the effect of interleukin-1 (3 pM) on CRF secretion. The effect of NG-nitro-L-arginine was prevented by pre-exposure of hypothalami to L-arginine (1 mM). We also studied whether the involvement of NO in this interleukin-1 effect could involve a prostaglandin action. The concurrent treatment with NG-nitro-L-arginine and indomethacin (14 microM)--an inhibitor of prostaglandin production--reduced interleukin-1-induced CRF release to the same level as NG-nitro-L-arginine alone, suggesting that prostaglandins might interact with NO on this interleukin-1 effect. These results suggest that NO plays a role in the in vitro stimulatory action of interleukin-1 on hypothalamic CRF secretion.
Sandi
C
C
Psychobiology Research Group, Cajal Institute, CSIC, Madrid, Spain.
Guaza
C
C
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D006454:Hemoglobins / Q000494:pharmacology; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D015918:Infusion Pumps, Implantable; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D006454:Hemoglobins; D007375:Interleukin-1; D011994:Recombinant Proteins; D019335:Nitroarginine; D009569:Nitric Oxide; D003346:Corticotropin-Releasing Hormone; D001120:Arginine; D007213:Indomethacin