Actions of Papaverine, Aspaminol and Bile Salts and Intracellular Cyclic AMP Level

Uruno, Tsutomu; Takayanagi, Issei; Tokunaga, Masako; Kubota, Keiichi; Takagi, Keijiro

doi:10.1254/jjp.24.681

Cited by 19 publications

(7 citation statements)

References 20 publications

(13 reference statements)

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“…Although papaverine increases the amount of cyclic AMP by inhibiting phosphodiesterase (Kukovetz & Poch, 1970;Poch & Kukovetz, 1971;Bar, 1974;Uruno et al, 1974;Takayanagi et al, 1978), a number of inconsistencies in the relationship between inhibition of phosphodiesterase and the relaxant effect of papaverine have been found (Andersson etal., 1977;Polson etal., 1978 (Fujiwara etal., 1982;Fujiwara & Kuriyama, 1983), and the contraction evoked by excess concentrations of K+ to influx of Ca2+ by activation of the voltagedependent Ca2+ channel. Both phenomena ceased in Ca2+-free EGTA-containing solution, or on treatment with papaverine.…”

Section: Discussionmentioning

confidence: 99%

Lack of a causal relationship between the vasodilator effect of papaverine and cyclic AMP production in the dog basilar artery

Fujioka

1984

British J Pharmacology

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1 The effects of papaverine and isoprenaline on smooth muscle cells of the dog basilar artery were investigated using radioimmunoassay, electrophysiological and isometric tension recording methods. For comparative purposes, the actions of these drugs on the guinea-pig basilar artery were also examined. 2 Papaverine and isoprenaline (1 pM and 10 tiM) increased the amount of cyclic AMP in both dog and guinea-pig basilar arteries. 3 Papaverine (up to 100 jM) and isoprenaline (up to I jM) had no effect on the membrane potential and membrane resistance measured by recording the amplitudes of the electrotonic potentials in smooth muscle cells of the dog and guinea-pig basilar arteries. 4 The action potential evoked by outward current pulses after pretreatment with tetraethylammonium chloride (5 -10 mM) was inhibited by papaverine (> 1 jiM) but not by isoprenaline (up to 10 jiM) in smooth muscle cells of the dog and guinea-pig basilar arteries. dependently. Isoprenaline (1 Mm) had only slight effects on the contraction evoked by low concentrations of 5-hydroxytryptamine (10 nM). 6 In the Ca2+-free solution containing EGTA (2mM), the contraction evoked by 5-hydroxytryptamine (10 Mm) or caffeine (10mM) was dose-dependently inhibited by papaverine (> 1 MM). However, isoprenaline (1 IM) had no effect on these contractions. 7 These results indicate that the vasodilator actions of papaverine on the dog basilar artery are mainly due to inhibition of the voltage-dependent influx of Ca2+ and also to inhibition of the receptor-activated release of Ca2+ stored in the cell. Since isoprenaline increased the cyclic AMP to the same extent as papaverine but had no effect on the electrical and mechanical responses, the inhibitory actions of papaverine on this tissue may not be causaly related to the increased levels of cyclic AMP induced by inhibition of phosphodiesterase.

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Section: Discussionmentioning

confidence: 99%

Lack of a causal relationship between the vasodilator effect of papaverine and cyclic AMP production in the dog basilar artery

Fujioka

1984

British J Pharmacology

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“…There is evidence that papaverine inhibits cyclic nucleotide phosphodiesterase activity in some muscles (Poch & Kukovetz, 1971; Urono, Takayanagi, Tokunaga, Kubota & Takagi, 1974;Miyamoto, Takayanagi, Ohkubo & Takagi, 1976) implicating a rise in cellular cyclic AMP concentration as the mediator of relaxation (Triner, Nahas, Vulliemoz, Overweg, Verosky, Habif & Ngai, 1971;Poch &I Umfahrer, 1976;Honeyman, Merriam & Fay, 1978). This analysis, however, is fraught with inconsistencies.…”

Section: Introductionmentioning

confidence: 99%

Inhibition by papaverine of calcium movements and tension in the smooth muscles of rat vas deferens and urinary bladder.

Huddart¹,

Langton²,

Saad³

1984

The Journal of Physiology

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SUMMARY1. Papaverine, up to 150 /M, was without effect on resting tension of vas deferens and urinary bladder smooth muscle strips, but caused a dose-dependent inhibition of the phasic component of the 100 mM-K contracture. At 150 FM, papaverine caused an 80 and 60 % inhibition ofphasic tension in vas deferens and urinary bladder muscle respectively.2. Papaverine caused a marked dose-dependent reduction in the tonic component of 100 mM-K contractures in both preparations. At 150 /M, papaverine often relaxed preparations below initial starting tension.3. Addition of 150 /ZM-papaverine to incubation media caused a fall of 25-30 % in 45Ca uptake by both preparations.4. Papaverine at 150 /LM caused a small fall in resting 45Ca efflux from vas deferens and a larger fall in efflux from bladder muscle. However, this papaverine concentration caused a large inhibition of the 45Ca uptake by and 45Ca efflux from both preparations when stimulated by high-K depolarization.5. Papaverine at 150 ,lM was without significant effect on Ca binding by either microsomes or mitochondria isolated from both vas deferens and urinary bladder smooth muscle.6. The main site of papaverine action appears to be on the Ca-influx mechanism responsible for regulating Ca entry during prolonged K depolarization.

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“…Such a nonspecific spasmolytic action of bile salts have also been demonstrated in the intestine (Kimura et al, 1967;Kubota et al, 1970;) and the uterus (Uruno et al, 1974(Uruno et al, , 1975. Deoxycholate and ursodeoxycholate accelerated the 45Ca-efflux from the gallbladder partly depolarized by potassium when the drugs were applied to the muscle during the later efflux phase where intracellularly bound calcium ions were effluxed (Fig.…”

Section: Discussionmentioning

confidence: 57%

“…Uruno et al (1974) showed that bile salts could inhibit cyclic AMP phosphodiesterase (PDE) activity, resulting in the accumulation of cytoplasmic cyclic AMP. Good correlation between the increment of cyclic AMP level and the relaxant effects of bile salts was also found in the rat uterus (Uruno et al, 1975).…”

Section: Introductionmentioning

confidence: 99%

Possible mechanisms of spasmolytic action of bile salts on the isolated guinea-pig gallbladder.

Sunagane

Kobori

Uruno

et al. 1990

Jpn. J. Smooth Muscle Res.

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Sunagane N., T. Kobori, T. Uruno and K. Kubota. Possible mechanisms of spasmolytic action of bile salts on the isolated guinea-pig gallbladder. The spasmolytic action of bile salts on gallbladder smooth muscle could explain the alleged relief of biliary colic seen during bile acid therapy. The mechanisms of spasmolytic action of bile salts, ursodeoxycholate and deoxycholate were studied in the isolated gallbladder of guinea-pigs.The bile salts accelerated the 45Ca-efflux from the gallbladder with synchronous relaxation and inhibited the cellular 45Ca-uptake by the depolarized muscle preparation. Further, they sensitively inhibited CaCl2-induced contraction of the depolarized muscle. The tissue cyclic AMP content of the gallbladder was significantly elevated by the bile salts. Dibutyryl cyclic AMP mimicked the effects of bile salts on the Ca-efflux and the muscle relaxation, but showed no effect on the cellular Ca-uptake. From these results, it is suggested that the bile salts produce the relaxant action through accelerating Ca-efflux, which is probably coupled with the elevation of the cellular cyclic AMP level, and through suppressing the Ca-influx across the cell membrane.

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Actions of Papaverine, Aspaminol and Bile Salts and Intracellular Cyclic AMP Level

Cited by 19 publications

References 20 publications

Lack of a causal relationship between the vasodilator effect of papaverine and cyclic AMP production in the dog basilar artery

Lack of a causal relationship between the vasodilator effect of papaverine and cyclic AMP production in the dog basilar artery

Inhibition by papaverine of calcium movements and tension in the smooth muscles of rat vas deferens and urinary bladder.

Possible mechanisms of spasmolytic action of bile salts on the isolated guinea-pig gallbladder.

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