Adenosine receptor‐mediated relaxation of guinea‐pig precontracted, isolated trachea

Losinski, Amanda; Alexander, Stephen

doi:10.1111/j.1476-5381.1995.tb15090.x

Cited by 23 publications

(19 citation statements)

References 15 publications

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“…This rank order of potency is identical to that at the A2b adenosine receptors of guinea-pig (Losinski et al, 1993) and rat cerebral cortex (Bazil & Minneman, 1986), although the absolute potencies of the adenosine analogues appeared highest in guinea-pig cerebellum. The antagonists investigated showed an identical rank order of potency (XAC>DPCPX>PD 115,199) when compared with guinea-pig cerebral cortex (Losinski et al, 1993), with, again, a slightly-enhanced affinity. DPCPX has been characterized as an Al-selective antagonist (Lee & Reddington, 1986;Bruns et al, 1987a;Lohse et al, 1987), with low affinity at Au, receptors.…”

Section: Discussionmentioning

confidence: 52%

Adenosine receptor‐induced second messenger production in adult guinea‐pig cerebellum

Hernández

Kendall

Alexander

1993

British J Pharmacology

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1 The effects of adenosine receptor agonists on cyclic nucleotides accumulation were investigated in adult guinea-pig cerebellar slices by use of radioactive precursors. 2 Adenosine elicited a rapid and maintained increase in cyclic AMP, that was fully reversed upon addition of adenosine deaminase. Adenosine analogues stimulated cyclic AMP generation up to 40 fold with the rank order of potency: 5'-N-ethylcarboxamidoadenosine (0.6 tM) > 2-chloroadenosine (6p1M)>adenosine (13 iM). CGS 21680 (10pM) elicited only a small stimulation (1.2 fold).3 The cyclic AMP response to NECA was reversed by the 1,3-dipropylxanthine-based adenosine receptor antagonists 8-[4-[[[[(2-aminoethyl) (PD 115,199) with estimated apparent inhibition constants of 15, 81 and 117nM, respectively. 4 Pretreatment with adenosine also potentiated the cyclic GMP response to sodium nitroprusside, abolishing the decline in [3H]-cyclic GMP observed with sodium nitroprusside alone, and allowing [3H]-cyclic GMP levels to be maintained for at least an additional 10 min. This potentiation was fully reversed by adenosine deaminase. 5 Adenosine analogues potentiated the sodium nitroprusside-elicited cyclic GMP generation with the rank order of potency: 5'-N-ethylcarboxamidoadenosine (0.7 JIM)> 2-chloroadenosine (6 JM)> adenosine (42 JIM). 6 NECA potentiation of cyclic GMP formation was reversed by the antagonists XAC, DPCPX and PD 115,199 with apparent inhibition constants of 17, 102 and 242 nM, respectively. 7 The similar potencies of adenosine analogues and xanthine antagonists for stimulation of cyclic AMP and potentiation of cyclic GMP lead to the suggestion that these phenomena are mediated through the same adenosine receptor, the A2b receptor. Furthermore, we suggest that potentiation of the sodium nitroprusside-induced cyclic GMP response may be mediated at the level of phosphodiesterase hydrolysis of the cyclic nucleotides.

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Section: Discussionmentioning

confidence: 52%

Adenosine receptor‐induced second messenger production in adult guinea‐pig cerebellum

Hernández

Kendall

Alexander

1993

British J Pharmacology

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“…We observed that relaxation by the extract of carbachol-precontracted trachea induced a small but significant increase of the cAMP levels. This could be due to the activation of b-adrenergic or adenosinic (Losinski & Alexander 1995) receptors but also to phosphodiesterase inhibition. The latter hypothesis would be consistent with the potentiating effect of the extract on isoprenaline (table 2).…”

Section: Discussionmentioning

confidence: 99%

“…B. Interaction with adenosinic receptors. The ability of xanthine amine congener, an adenosinic antagonist Ukena et al 1986), of inhibiting the relaxant of effect of the extract, b-hydrastine and canadaline (table 1), indicated a possible involvement of adenosinic receptors, which play an important role in guinea pig trachea relaxation (Losinski & Alexander 1995;Hadjkaddour et al 1996).…”

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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“…A 2 receptors were identified in tracheal smooth muscle by pharmacological analysis (Brackett et al, 1990;Losinski and Alexander, 1995). Ghai et al (1987) presented evidence for both A 1 and A 2 receptors on guinea pig tracheal smooth muscle.…”

Section: B Smooth Muscle and Its Innervationmentioning

confidence: 99%

Purinergic Signaling in the Airways

Burnstock

Brouns²,

Adriaensen³

et al. 2012

Pharmacol Rev

174

158

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Adenosine receptor‐mediated relaxation of guinea‐pig precontracted, isolated trachea

Cited by 23 publications

References 15 publications

Adenosine receptor‐induced second messenger production in adult guinea‐pig cerebellum

Adenosine receptor‐induced second messenger production in adult guinea‐pig cerebellum

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

Purinergic Signaling in the Airways

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