Effects of 8-iso-prostaglandin E2 and 8-iso-prostaglandin F2 alpha on the release of noradrenaline from the isolated rat stomach.
In the present experiment, we examined the effect of 8-iso-prostaglandin E(2) and 8-iso-prostaglandin F(2 alpha) on the release of noradrenaline from the isolated rat stomach. The postganglionic sympathetic nerves were electrically stimulated twice at 1 Hz for 1 min and test reagents were added during the second stimulation. 8-Iso-prostaglandin E(2) (10(-8)-10(-6) M) and 8-iso-prostaglandin F(2 alpha) (10(-7)-10(-5) M) dose-dependently reduced the evoked noradrenaline release, and these inhibitory potencies were as follows: 8-iso-prostaglandin E(2)>8-iso-prostaglandin F(2 alpha). The inhibitory effect of 8-iso-prostaglandin F(2 alpha), but not 8-iso-prostaglandin E(2), was abolished by 10(-6) M SQ-29548 ([1S-[1 alpha,2 alpha(Z),3 alpha,4 alpha]]-7-[3-[[2-[(phenylamino)carbonyl]hydrazino] methyl]-7-oxabicyclo[2,2,1]hept-2-yl]-5-heptenoic acid) (a prostanoid TP receptor antagonist). On the other hand, the inhibitory effect of 8-iso-prostaglandin E(2) was abolished by 10(-5) M AH-6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid) (a prostanoid EP receptor antagonist), which also attenuated the inhibitory effects of ONO-AE-248 (16S-9-deoxy-9 beta-chloro-15-deoxy-16-hydroxy-17,17-trimethylene 19, 20-didehydro prostaglandin F(2)) (a selective EP(3) receptor agonist) on the evoked release of noradrenaline. The inhibitory effect of 8-iso-prostaglandin F(2 alpha), but not 8-iso-prostaglandin E(2), was abolished by pertussis toxin. These results suggest that 8-iso-prostaglandin F(2 alpha) inhibits noradrenaline release through TP receptors, whereas 8-iso-prostaglandin E(2) seems to inhibit noradrenaline release through EP(3) receptors, located on the gastric sympathetic nerve terminals in rats.
Nakamura
Kumiko
K
Department of Pharmacology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
Okada
Shoshiro
S
Ono
Kaori
K
Yokotani
Kunihiko
K
D000818:Animals; D015237:Dinoprost / Q000031:analogs & derivatives*; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D028441:F2-Isoprostanes / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism; D028421:Isoprostanes / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects*
D028441:F2-Isoprostanes; D028421:Isoprostanes; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D015232:Dinoprostone; C011987:8-isoprostaglandin E2; D009638:Norepinephrine