Persistent effects of interleukin-1 on smooth muscle preparations from adrenalectomized rats: implications for increased phospholipase-A2 activity via stimulation of 5-lipoxygenase.
Human recombinant interleukin-1 beta (hrIL-1 beta) potentiated CaCl2-induced contractions of isolated stomach strip preparations from adrenalectomized rats (ADXSS). Associated with this effect were increased prostaglandin E2 and peptidyl leukotriene (LT) synthesis. Unlike preparations from normal rat stomach strips or sham-operated animals, tissue responses and eicosanoid production of ADXSS failed to return to pre-hrIL-1 beta control levels after washout of the interleukin, these effects being abrogated by the lipoxygenase inhibitor nordihydroguaiaretic acid. Additionally, the LTD4 antagonist FPL55712 also prevented the increase in contraction and prostaglandin E2 synthesis caused by hrIL-1 beta without decreasing peptidyl LT synthesis. In separate experiments, hrIL-1 beta failed to increase the recovery of arachidonic acid-induced contractions after aspirin pretreatment in both ADXSS and rat stomach strips. The data indicate that the effects caused by hrIL-1 beta on ADXSS are possibly the result of an exacerbated phospholipase A2 activity particularly inasmuch as increases in cellular cyclooxygenase synthesis are unlikely in this experimental system. It appears likely that a peptidyl LT is involved in this process. Elevation of phospholipase A2 activity by interleukin-1 like drugs may be an important factor limiting the use of these agents as adjuvants particularly in patients with low blood glucocorticoid levels.
Mugridge
K G
KG
Sclavo Research Centre, Laboratory of Pharmacology, Siena, Italy.
Perretti
M
M
Becherucci
C
C
Parente
L
L
D000315:Adrenalectomy; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002867:Chromones / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D015289:Leukotrienes / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013189:SRS-A / Q000494:pharmacology; D013268:Stimulation, Chemical; D013270:Stomach / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D001095:Arachidonic Acids; D002867:Chromones; D007375:Interleukin-1; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011994:Recombinant Proteins; D013189:SRS-A; D016718:Arachidonic Acid; D009637:Masoprocol; C006312:FPL 55712; D001094:Arachidonate 5-Lipoxygenase; D010741:Phospholipases A; D054467:Phospholipases A2; D001241:Aspirin; D007213:Indomethacin