Effects of 8- iso-prostaglandin E 2 and 8- iso-prostaglandin F 2α on the release of noradrenaline from the isolated rat stomach

Abstract

In the present experiment, we examined the effect of 8- iso-prostaglandin E 2 and 8- iso-prostaglandin F 2α 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 2α (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 2α. The inhibitory effect of 8- iso-prostaglandin F 2α, but not 8- iso-prostaglandin E 2, was abolished by 10 −6 M SQ-29548 ([1 S-[1α,2α( Z),3α,4α]]-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 (16 S-9-deoxy-9β-chloro-15-deoxy-16-hyfroxy-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 2α, but not 8- iso-prostaglandin E 2, was abolished by pertussis toxin. These results suggest that 8- iso-prostaglandin F 2α 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.