|Budget Amount *help
¥1,700,000 (Direct Cost : ¥1,700,000)
Fiscal Year 1991 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1990 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Effects on the contraction of vas deferens induced by nerve stimulation : In guinea pig vas deferens, both pre- and post-ganglionic stimulations of hypogastric nerve induced a biphasic contraction consisting of a rapig transient phas and delayed tonic Phase. Indomethacin partly inhibited the contraction induced by pre-ganglionic stimulation, but not the responses by post-ganglionic stimulation. The indomethacin inhibition was reversed by PGE_2- PGE_2 also delayed the onset of phasic contraction and increased the height of both phasic and tonic contractions, and significantly enhanced the contraction induced by authentic ATP and norepinephrine. The contraction induced by pre-ganglionic stimulation was inhibited by mepacrine and PGE_2 receptor antagonist, SC19220. PGE_2 and arachidonic acid reversed these inhibition. The findings suggest that endogenous PGE_2 is important in neurotransmission in the plevic ganglion of guinea pig.
Effects on the release of ACh from the myenteric plexus of
guinea pig ileum : The amount of ACh released in response to nicotine or substance P was depressed to about 40% of control by indomethacin, whereas that induced by 5-HT or electrical field stimulaltion(EFS)was not affected. The inhibitory effect of indomethacin were reversed by PGE_2. Mepacrine, an inhibitor of pbospbolipase A_2, depressed the release of ACh by nicotine and substance P to the same extent as indomethacin. OP-41483, an analogue of PGI_2, recovered inhibited nicotine-induced release more effectively than PGE_2. This effect was abolished by H-89, an A-kinase inhibitor. PGD_2, PGF_<2alpha> and TXA_2 analogue were ineffective. PGI_2 was released during incubation of preparation in the amount as much as 5 times of PGE_2. These results indicate that both endogenous PGI_2 and PGE_2 regulate the excitability of cholinergic neurons in the myenteric plexus and that the effects are mediated by the activation of intracellular cyclic AMP system. The ACh release by EFS was inhibited by 5-lipooxygenase inhibitors but not by 12-lipoxygenase inhibitor. The inhibitory effects were reversed by arachidonic acid, 5-HETE, LTD_4 and LTE_4, but not by LTB_4 and LTC_4, indicating the regulation5-lipoxygenase metavolites on efs induced ach release.
In conclusion, many prostanoias contribute for maintaing the activity of the myeyerixc plecus of guinea pig iluem, but the kind of prostanoid concerned may diffe with different stimuli applied to nerve.