On the mechanism of vasodilating action of berberine: possible role of inositol lipid signaling system.
We have studied the effect of the alkaloid berberine on the contraction of guinea pig aortic strips induced by various stimuli. Berberine (25-200 microM) inhibited the response of the strips to norepinephrine and histamine, but did not decrease the high K(+)-elicited contraction. The antagonism of berberine was not competitive because in the presence of the alkaloid, maximum response to agonists could not be obtained. Analysis of the drug's effect on the time course of norepinephrine-induced contraction showed that berberine reduced both the rate and the relative contribution to developed tension of the initial, rapid phase, whereas the slow, later component was less affected. Berberine inhibited the response of aortic strips incubated in 0 mM Ca++ to norepinephrine, but did not reduce caffeine-induced contraction and also inhibited phospholipase C-activated contractile response, which has been ascribed to production of inositol phosphate-3 in smooth muscle cells. In cultured arterial smooth muscle cells (A7r5 line), the alkaloid did not significantly decrease the production of inositol phosphates activated by Arg8-vasopressin. The pattern of berberine action is difficult to reconcile with an involvement of the contractile machinery and suggests that the drug has no effect on the voltage-operated calcium channels. Although an antagonism at the receptors or an increase of cyclic AMP or cyclic GMP cannot be completely excluded, we suggest that at least one component of the berberine inhibitory effect may be due to its action on some step of the chain of events linking receptors to contractile response.
Bova
S
S
University of Padova, Department of Pharmacology, Largo E. Meneghetti, Italy.
Padrini
R
R
Goldman
W F
WF
Berman
D M
DM
Cargnelli
G
G
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001599:Berberine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D007295:Inositol Phosphates / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D007295:Inositol Phosphates; D001599:Berberine; D001127:Arginine Vasopressin; D011188:Potassium; D009638:Norepinephrine