Inhibition by interleukin-1 beta of noradrenaline release in rat spleen: involvement of lymphocytes, NO and opioid receptors.
Effects of indomethacin, N omega-nitro-L-arginine (NNA) and naloxone, and of pretreatment with cyclophosphamide (CY), on the interleukin (IL)-1 beta induced inhibition of exocytotic noradrenaline release were investigated in the isolated, vascularly perfused spleen of the rat. Neurotransmitter release was evoked by perivascular electrical stimulation (4 Hz) and the overflow of endogenous noradrenaline was determined by HPLC with electrochemical detection. Perfusion of the spleen with Tyrode's solution containing IL-1 beta (100 pg/ml) for 90 min caused an inhibition of the stimulation-evoked noradrenaline overflow which persisted for at least 20 min after washout of the IL. The evoked overflow was reduced in the presence of NNA 30 mumol/l, but remained unaffected by indomethacin 3 mumol/l, naloxone 0.1 mumol/l or treatment of the rats with CY (250 mg/kg). The opioid agonist etorphine 10 mumol/l inhibited the evoked overflow of noradrenaline and this effect was prevented by naloxone 0.1 mumol/l. The inhibition of evoked overflow by IL-1 beta was not affected by indomethacin but was reduced or even prevented in the presence of NNA or naloxone, or after lymphocyte depletion of spleens by CY. The results are compatible with the idea that in the rat spleen exocytotic noradrenaline release is accompanied by a concomitant secretion of a nitric oxide (NO)-like compound which, in turn, reinforces noradrenaline release, and that the release can be inhibited via prejunctional opioid receptors. The IL-1 beta induced inhibition of evoked release appears to be a complex process which involves as one of many steps a decrease of the facilitatory NO-like compound and the release of endogenous opioids probably from spleen lymphocytes.
Bognar
I T
IT
Pharmakologisches Institut der Universität, Mainz, Germany.
Albrecht
S A
SA
Farasaty
M
M
Fuder
H
H
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine; D009638:Norepinephrine / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D007375:Interleukin-1; D011957:Receptors, Opioid; D019335:Nitroarginine; D009569:Nitric Oxide; D009270:Naloxone; D003520:Cyclophosphamide; D001120:Arginine; D009638:Norepinephrine; D007213:Indomethacin