ISSN:
1432-1912
Keywords:
Prostacyclin
;
15-hydroperoxyarachidonic acid
;
9,11-azoprosta-5,13-dienoic acid
;
11,9-epoxyiminoprosta-5,13-dienoic aicd smooth muscle contraction
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 1. Using sensitive and specific radioimmunoassays release of prostaglandins (PGs) E2, F2α, 6-keto-F1α and thromboxane B2 (TXB2) from rabbit splenic capsular strips was determined. 2. Contraction of the strips by noradrenaline increased the release of 6-keto-PGF1α, PGE2, PGF2α and TXB2 as compared to basal conditions. Indomethacin inhibited synthesis and release of PGs and TXB2 and simultaneously increased noradrenaline-induced contractions. 3. Arachidonic acid and dihomo-γ-linolenic acid, both substrates for the enzyme fatty acid cyclooxygenase, dose-dependently antagonized noradrenaline-induced contractions. On the other hand, fatty acids, which are not substrates for the cyclooxygenase, had no effect. Pretreatment of the smooth muscle strips with indomethacin inhibited the effect of arachidonic acid and dihomo-γ-linolenic acid. 4. The PG endoperoxides PGG2 and PGH2 as well as their derivative prostacyclin (PGI2) were more effective than arachidonic acid as inhibitors of noradrenaline-induced contractions. The stable degradation product of PGI2, 6-keto-PGF1α, did not influence the contractions. The effects of the PG endoperoxides and PGI2 were not inhibited by indomethacin. 5. The 6(9)oxycyclase inhibitor 9,11-azoprosta-5,13-dienoic acid antagonized the inhibitory effects of arachidonic acid and PGG2 on the contractions, but did not modify the effect of PGI2. 6. Inhibitors of PGI2 synthesis such as 15-hydroperoxyarachidonic acid and 9,11-azoprosta-5,13-dienoic acid increased, like indomethacin, noradrenaline-induced contractions of the rabbit splenic capsular strips in the absence of exogenous PG precursors. On the other hand, a specific inhibitor of TX synthesis, 11,9-epoxyiminoprosta-5,13-dienoic acid, was without effect on the contractions. 7. The results are compatible with the view that endogenous PGI2 modulates the contractile response of rabbit splenic capsular smooth muscle to noradrenaline. The hypothetical PGI2 receptor on the smooth muscle seems to resemble in its specificity the PGI2 receptor on thrombocytes of various species as only PGE1 in higher concentrations has effects comparable to PGI2. 8. Besides the presynaptic inhibition of noradrenaline release by PGE the postsynaptic inhibition of noradrenaline-induced smooth muscle contraction by endogenous PGI2 might represent, at least in vitro, another feed-back mechanism to attenuate the effects of sympathetic nerve stimulation. Synthesis and release of antiaggregatory and contraction-inhibiting PGI2 by splenic tissue might play a role in the function of the spleen as a storage site for thrombocytes.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00499154
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