Actinomycin D blocks interleukin-1 alpha-induced pial arteriolar dilation and increased prostanoid production in newborn pigs.
Effects of protein synthesis and cyclooxygenase inhibitors on interleukin-1 alpha (IL-1 alpha)- and histamine-induced pial arteriolar dilation and cerebrospinal fluid (CSF) prostanoid increases were examined in anesthetized piglets using closed cranial windows. Topical IL-1 alpha (10.8 micrograms) increased pial arteriolar diameter from 15 to 30 min after its infusion, and enhanced CSF prostanoids. Topical protein synthesis inhibitor, actinomycin D, at a concentration of 10(-8) M attenuated and 10(-6) M completely blocked both IL-1 alpha-induced vasodilation and CSF prostanoid increase. Inhibition of prostaglandin H synthases with indomethacin blocked both vasodilation and CSF prostanoid increase by IL-1 alpha. Topical histamine (10(-6) M) also increased pial arteriolar diameter and CSF prostanoids but without the delay seen between IL-1 alpha infusion and responses. These histamine effects were not modified by coinfusion of actinomycin D but blocked by indomethacin. These results suggest that, although IL-1 alpha and histamine do share the same mechanism insofar as activation of prostaglandin synthesis is concerned, an additional step appears to be involved for IL-1 alpha, likely involving de novo protein synthesis.
Shibata
M
M
Department of Physiology, University of Tennessee, Memphis 38163.
Mirro
R
R
Armstead
W M
WM
Leffler
C W
CW
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001784:Blood Gas Analysis; D003609:Dactinomycin / Q000494:pharmacology*; D005260:Female; D006632:Histamine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D007375:Interleukin-1; D011453:Prostaglandins; D011994:Recombinant Proteins; D003609:Dactinomycin; D006632:Histamine; D007213:Indomethacin