Involvement of cAMP and β‐adrenoceptors in the relaxing effect elicited by flavonoids on rat uterine smooth muscle

Abstract

1. The effect of the flavonoids genistein (3-100 microM), kaempferol (3-60 microM) and quercetin (1-100 microM) on KCl (60 mM)-induced tonic contraction in rat smooth muscle was assayed. In the same way, the modification of these effects in the presence of an inhibitor of protein kinase (PKA) (Rp-cAMPS), an inhibitor of phosphodiesterase (papaverine) and beta-adrenoreceptor blocking agents (propranolol and atenolol) was studied. 2. The flavonoids totally relaxed the KCl-induced tonic contraction (IC50: genistein 20.2 +/- 2.0 microM, n = 11; kaempferol 10.1 +/- 1.6 microM, n = 8; quercetin 13.2 +/- 1.2 microM, n = 8). 3. The incubation with Rp-cAMPS (10 and 100 microM) 30 min prior to KCl shifted the dose-response curve of the flavonoids to the right, increasing their IC50 up to 27.8 +/- 3.8 and 31.9 +/- 7.3 microM, respectively, for genistein; 24.7 +/- 0.2 and 19.6 +/- 4.9 microM, respectively, for kaempferol; 18.8 +/- 2.2 and 18.4 +/- 1.5 microM, respectively, for quercetin. 4. Papaverine (3-100 microM) also relaxed the contraction induced by KCl and this effect was significantly displaced to the right with Rp-cAMPS (10 microM) (IC50 12.1 +/- 2.2 vs. 16.5 +/- 3.1 microM). Papaverine (3 microM) added to the organ bath 15 min before the contractile agent increased the relaxing effect of the flavonoids and significantly decreased their IC50 (genistein 20.2 +/- 2.0 vs. 9.8 +/- 1.4 microM; kaempferol 10.1 +/- 1.6 vs. 6.6 +/- 0.7 microM; quercetin 13.2 +/- 1.2 vs. 7.8 +/- 1.4 microM). 5. The incubation with atenolol (10 microM) did not alter the relaxing effect of the flavonoids. In the same experimental conditions, propranolol (10 microM) did not modify the effect of genistein and kaempferol, but shifted the response curve of quercetin significantly to the right (13.2 +/- 1.2 vs. 17.7 +/- 3.4 microM). 6. The results suggest that genistein, kaempferol and quercetin produced the relaxation of uterine smooth muscle by increasing intracellular cAMP. Beta-adrenoceptors could also be involved in the effect of quercetin.

<i>In vivo</i> and <i>in vitro</i> effects of <i>Bidens pilosa</i> l. (asteraceae) leaf aqueous and ethanol extracts on primed-oestrogenized rat uterine muscle.

“…These differences could be due to the existence of active substance(s) in B. pilosa's leaves, which have a variable solubility coefficient (difference in polarity) of the molecules extracted with the solvent used for extraction (water and ethanol). Natural estrogenic-like compounds are generally more extractable in ethanol than in water (Circosta et (Revuelta et al, 1999). This dual effect is in accordance with our results could be due to the nature of solvent used for extraction or the instability of polyacetylene bioactivity (Krettli et al, 2001).…”

Intracoronary Genistein Acutely Increases Coronary Blood Flow in Anesthetized Pigs through β-Adrenergic Mediated Nitric Oxide Release and Estrogenic Receptors

“…This hypothesis can be further confirmed by the results obtained in experiments performed with butoxamine, which abolished the effect of genistein on NO production, and by the analysis of the level of phosphorylation of ERK1/2, Akt, and p38. It is noteworthy that these results are in agreement with in vitro studies evidencing an interrelation between flavonoids and ␤-adrenoceptors (31,42).…”

“…For instance, in rat aortic rings, genistein potentiated the relaxation induced by isoproterenol, an effect that could be related to the inhibition of cAMP-phosphodiesterase activity (17). Furthermore, both cAMP and ␤-adrenoceptors have been related to the relaxing effect elicited by flavonoids on rat uterine smooth muscle (42).…”

“…The mean pH, PO 2 , and PCO 2 of arterial blood were 7.40 Ϯ 0.03 (7.39 -7.43), 118.3 Ϯ 9.3 (102-142) mm Hg and 39.7 Ϯ 1.1 (37)(38)(39)(40)(41)(42) mm Hg and the hematocrit was 38.5% Ϯ 1.6 (38 -40).…”

The Small Polyphenolic Molecule Kaempferol Increases Cellular Energy Expenditure and Thyroid Hormone Activation

“…2A). Indeed, it has been observed previously that KPF increases intracellular cAMP concentrations in colonocytes (26) and uterine smooth myocytes (27), possibly through inhibition of phosphodiesterases (28). While we have no evidence of direct activation of adenylyl cyclases by KPF (data not shown), the structural similarity between KPF and forskolin, also a small polycyclic molecule extracted from plants that directly activates adenylyl cyclase, is notable (29).…”