Inhibition of cyclic-3?,5?-nucleotide-phosphodiesterase as a possible mode of action of papaverine and similarly acting drugs

Kukovetz, W. R.; Pöch, G.

doi:10.1007/bf00999402

Cited by 250 publications

(46 citation statements)

References 7 publications

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“…However, up to our knowledge, berberine and the other alkaloids examined here have not been reported to possess this property, even if structurally related substances such as papaverine ???? (Karlsson et al 1988;Kraupp et al 1994;Kukovetz & Poch 1970;Poch & Kukovetz 1971;Hanna et al 1972;Berndt et al 1976). …”

Section: Discussionmentioning

confidence: 99%

Relaxant Effects of Hydrastis canadensis L. and its Major Alkaloids on Guinea Pig Isolated Trachea

Abdel‐Haq

Cometa

Palmery

et al. 2000

Pharmacology & Toxicology

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Hydrastis or goldenseal, one of the most popular medicinal herbs in the U.S.A., is used in mild pathological conditions like cold and flu, based on the pharmacological properties of its active components, berberine (anticholinergic, antisecretory, and antimicrobial) and b-hydrastine (astringent). We previously reported the relaxant effect of a total ethanolic extract of hydrastis on carbachol precontracted isolated guinea pig trachea, and with the present study, using the same experimental model, we aimed at evaluating the contribution of its major alkaloids, berberine, b-hydrastine, canadine and canadaline to the total effect. Furthermore, using specific pharmacological tools, like timolol and xanthine amine congener, we attempted to elucidate its mechanism of action. The EC 50 of berberine, b-hydrastine, canadine and canadaline, were 34.2∫0.6, 72.8∫0.6, 11.9∫1.2 and 2.4∫0.8 mg/ml, respectively. Timolol effectively antagonized the effect of canadine (EC 50 Ω19.7∫3.0 mg/ml) and canadaline (EC 50 Ω17.1∫1.2 mg/ml) but not that of berberine and b-hydrastine, while xanthine amine congener antagonized the effect of b-hydrastine (EC 50 Ω149.9∫35.3 mg/ml) and canadaline (EC 50 Ω 26.1∫3.0 mg/ml) but not that of berberine and canadine. Besides, the hydrastis extract, at concentrations between 0.01 and 0.1 mg/ml, potentiated the relaxant effect of isoprenaline on carbachol-precontracted isolated guinea pig trachea. These data, which are insufficient to draw definite mechanistic conclusions, indicate that the aforementioned alkaloids may act by interacting with adrenergic and adenosinic receptors.Hydrastis or goldenseal, i.e. the rhizome and roots of Hydrastis canadensis L., is a common medicinal herb (Winslow & Kroll 1998), often used, alone or in association with other vegetable drugs, for the treatment of mild pathological conditions such as colds and flu (Turow 1997; O'Mathú na 1998). The rationale for this application derives from the current pharmacological knowledge about its major active components, berberine (anticholinergic (Tsai & Ochillo 1991), antisecretory (Tai et al. 1981Zhu &Ahrens 1983) and antimicrobial (Amin et al. 1969;Pepeljnjak & Petricic 1992; Tang & Eisenbrand 1992;Reynolds 1996)) and b-hydrastine (astringent (Tyler et al. 1981) and antitussive (Karlsson et al. 1988)).Since we previously reported the relaxing effect of Hydrastis canadensis on isolated guinea pig trachea (Cometa et al. 1998), with the present study and using the same experimental model (Abdel-Haq et al. 2000), we aimed at evaluating the contribution of its major alkaloids, berberine, b-hydrastine, canadine and canadaline (Leone et al. 1996) to the total effect. In addition, using specific pharmacological tools, we attempted to elucidate the mechanism of action of this medicinal herb, the second or third most popular in the USA (as stated by the National Toxicology Program of the NIH), on the respiratory tract.Author for correspondence: Luciano Saso, Department of Pharmacology of Natural Substances and General Physiology, Un...

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Section: Discussionmentioning

confidence: 99%

Relaxant Effects of Hydrastis canadensis L. and its Major Alkaloids on Guinea Pig Isolated Trachea

Abdel‐Haq

Cometa

Palmery

et al. 2000

Pharmacology & Toxicology

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“…It is a well established fact that such an increase in the cyclic AMP level in the vasculature may produce vasodilatation (Kukovetz & Poch, 1970;Triner, Vulliemoz, Verosky, Habib & Nahas, 1972;Andersson, 1973;Namm & Leader, 1976).…”

Section: Effect Of Non-steroidal Anti-inflammatory Agents On the Reacmentioning

confidence: 99%

Myocardial Synthesis of Prostaglandin‐like Substances and Coronary Reactions to Cardiostimulation and to Hypoxia

Sunahara

Talesnik

1979

British J Pharmacology

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1Continuous recording of cardiac contractions and coronary flow from isolated perfused hearts of rats permitted the study of coronary reactions to: (a) cardiostimulation induced by single doses or slow infusions of noradrenaline, CaCl2, glucagon or electrically induced tachycardia; (b) short interruptions of coronary inflow (hypoxia). 2 Except during tachycardia the heart rate was kept constant at 210 beats/min by electrical pacing. 3 Metabolic coronary vasodilatation (MCD) resulting from cardiac hyperactivity induced by noradrenaline, Ca2 +, tachycardia or glucagon was inhibited by administration of prostaglandin E2. Reactive hyperaemia response to hypoxia was unaffected by prostaglandin administration. 4 Inhibition of MCD could also be obtained by prolonged infusion with arachidonic acid (1.6 x 10'-M), presumably by its conversion into prostaglandin-like substance since arachidonic acid failed to block MCD in hearts from rats pretreated with non-steroidal anti-inflammatory drugs (indomethacin, naproxen, phenylbutazone). 5 Reactive hyperaemia was unaffected either by arachidonic acid or by blockade of the synthesis of prostaglandin-like substances by anti-inflammatory drugs. 6 Since prostaglandin synthetase inhibition does not prevent but may enhance MCD, we do not adtocate prostaglandin-like substances as agents directly responsible for the coronary vasodilatation that follows cardiac hyperactivity. 7 We postulate that cardiac overproduction of prostaglandins may lead to a failure in the adaptive coronary flow response to cardiac hyperactivity (coronary insufficiency?).

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“…The specificity offorskolin as an activator ofadenylate cyclase (see Daly, 1984) and the finding that this diterpene, in concentrations similar to those used in the present work, increases cyclic AMP levels in frog sciatic nerves (Kilmer & Carlsen, 1984), strongly suggest that the enhancement of TTX-induced axonal block, caused by forskolin, is mediated by increases in intra-axonal cyclic AMP content. The enhancement of TTX-induced axonal block caused by papaverine may be attributed to its ability to inhibit phosphodiesterases (Kukovetz & Poch, 1970) and thus to increase cyclic AMP levels. However, papaverine is also an inhibitor of the uptake of adenosine (Huang & Daly, 1974), which is released from nerve fibres on electrical stimulation (Maire et al, 1982) and enhances TTXinduced axonal block (Ribeiro & Sebastiao, 1984).…”

Section: Discussionmentioning

confidence: 99%

“…It therefore seemed of interest to investigate the effect offorskolin on nerve conduction in preparations partially blocked by TTX. The effect of papaverine, a non-xanthine phosphodiesterase inhibitor (Kukovetz & Poch, 1970), on TTX-induced axonal block was also investigated.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of forskolin and papaverine on nerve conduction partially blocked by tetrodotoxin in the frog sciatic nerve

Ribeiro

Sebastião

1985

British J Pharmacology

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Inhibition of cyclic-3?,5?-nucleotide-phosphodiesterase as a possible mode of action of papaverine and similarly acting drugs

Cited by 250 publications

References 7 publications

Relaxant Effects of Hydrastis canadensis L. and its Major Alkaloids on Guinea Pig Isolated Trachea

Relaxant Effects of Hydrastis canadensis L. and its Major Alkaloids on Guinea Pig Isolated Trachea

Myocardial Synthesis of Prostaglandin‐like Substances and Coronary Reactions to Cardiostimulation and to Hypoxia

Inhibitory effects of forskolin and papaverine on nerve conduction partially blocked by tetrodotoxin in the frog sciatic nerve

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