Effects of 8-iso-prostaglandin E2 and 8-iso-prostaglandin F2α 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-2alpha 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-2alpha (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-2alpha. The inhibitory effect of 8-iso-prostaglandin F-2alpha, but not 8-iso-prostaglandin E-2, was abolished by 10(-6)M SQ-29548 ([1S-[1alpha,2alpha(Z),3alpha,4alpha]]-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-9beta-chloro-15-deoxy-16-hyfroxy-17,17-trimethylene 19, 20-didehydro prostaglandin F-2) (a selective EP3 receptor agonist) on the evoked release of noradrenaline. The inhibitory effect of 8-iso-prostaglandin F2,, but not 8-iso-prostaglandin E2, was abolished by pertussis toxin. These results suggest that 8-iso-prostaglandin F-2alpha inhibits noradrenaline release through TP receptors, whereas 8-iso-prostaglandin E-2 seems to inhibit noradrenaline release through EP3 receptors, located on the gastric sympathetic nerve terminals in rats. (C) 2003 Elsevier Science B.V All rights reserved.