Effects of 8-iso-prostaglandin E2 and 8-iso-prostaglandin F2α on the release of noradrenaline from the isolated rat stomach

• Published in: European journal of pharmacology Vol. 470; no. 1-2; pp. 73 - 78
• Main Authors: NAKAMURA, Kumiko, OKADA, Shoshiro, ONO, Kaori, YOKOTANI, Kunihiko
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 30.05.2003
• Subjects: Animals; Biological and medical sciences; Dinoprost - analogs & derivatives; Dinoprostone - analogs & derivatives; Dinoprostone - pharmacology; Dose-Response Relationship, Drug; F2-Isoprostanes - pharmacology; Gastric Mucosa - metabolism; Isoprostanes - pharmacology; Male; Medical sciences; Norepinephrine - antagonists & inhibitors; Norepinephrine - metabolism; Rats; Rats, Wistar; Stomach - drug effects; rat; Pertussis toxin; 8-Iso-prostaglandin E2; 8-Iso-prostaglandin F2α; Prostanoid EP3 receptor; TP receptor; Noradrenaline release; Stomach
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(03)01756-4

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.