Stimulatory effect of paeoniflorin on the release of noradrenaline from ileal synaptosomes of guinea-pig in-vitro

Abstract

The effect of paeoniflorin (an active principle of Paeoniae Radix, commonly used in traditional Chinese medicine) on the release of noradrenaline (norepineprhine) from nerve terminals was investigated using guinea-pig isolated ileal synaptosomes. Release was determined as the amount of noradrenaline, quantified by high-performance liquid chromatography-electrochemical detection, from samples incubated with paeoniflorin or vehicle. Paeoniflorin stimulated the release of noradrenaline in a concentration-dependent manner without an effect on the level of lactate dehydrogenase in the bathing medium. Tetrodotoxin abolished the action of paeoniflorin at concentrations sufficient to block sodium channels. The depolarizing effect of paeoniflorin on the membrane potential was also illustrated by a concentration-dependent increase in the fluorescence of bisoxonol. Moreover, the effect of paeoniflorin on bisoxonol fluorescence in ileal synaptosomes seems more potent than that of 4-aminopyridine. That paeoniflorin causes influx of calcium ions via the depolarization of nerve terminals could be considered. The noradrenaline-releasing action of paeoniflorin was abolished by removal of calcium chloride from the bathing medium. This action of paeoniflorin was also attenuated by Rp-cAMP atconcentrations sufficientto inhibitthe action of cyclicAMP. Therefore, paeoniflorin could induce a calcium-dependent and cyclic-AMP-related release of noradrenaline from sympathetic nerve terminals of guinea-pig ileum. Guanethidine inhibited the noradrenaline-releasing action of paeoniflorin in a concentration-dependent manner. The effect of paeoniflorin on the increase of bisoxonol fluorescence was not modified by atropine. Release of noradrenaline by paeoniflorin from noradrenergic nerve terminals was characterized. These findings suggest that paeoniflorin can stimulate tetrodotoxin-sensitive depolarization of membranes to result in a calcium-dependent and cyclic-AMP-related release of noradrenaline from noradrenergic nerve terminals.

Effects and mechanisms of Paeoniflorin, a bioactive glucoside from paeony root, on adjuvant arthritis in rats

“…PF can stimulate cAMP-related release of noradrenaline from noradrenergic nerve terminals [32]. We also found abnormal alterations in the G protein cAMP signaling cascade in synoviocytes of rats with collagen-induced arthritis, which could be modulated by TGP containing PF as the principle bioactive component [15].…”

Determination of paeoniflorin in rat hippocampus by high-performance liquid chromatography after intravenous administration of Paeoniae Radix extract

“…1), a characteristic monoterpene glucoside isolated from the root of P. lactiflora in 1963 [1], is one of the bioactive components in Paeoniae Radix. It has been reported that paeoniflorin exhibits many pharmacological effects such as anti-flammatory, anti-allergic effects [2], anti-hyperglycemic effects [3], anti-thrombosis effects [4], neuromuscular blocking [5][6][7][8][9], stimulating the release of noradrenaline [10], and enhancing glucose uptake [11].…”

Effects of cerebral ischemia-reperfusion on pharmacokinetic fate of paeoniflorin after intravenous administration of Paeoniae Radix extract in rats

“…It has been reported that paeoniflorin and/or Paeoniae Radix exhibit many pharmacological effects such as anti-inflammatory and antiallergic effects (Yamahara et al, 1982), antihyperglycemic effects (Hsu et al, 1997), analgesic effects (Sugishita et al, 1984), neuromuscular blocking (Kimura et al, 1984;Kimura et al, 1985a,b;Kimura et al, 1986;Dezaki et al, 1996), cognition-enhancing (Ohta et al, 1993a,b,c;Ohta et al, 1994;Watanabe, 1997), and inhibition of steroid protein binding (Tamaya et al, 1986). In addition, recent studies indicated 0378 their anti-thrombosis effects (Ye et al, 2001), stimulating the release of noradrenaline (Liu et al, 2002), anti-hypotension (Cheng et al, 1999) via activation of adenosine A-1 receptor (Lai et al, 1998), and enhancing glucose uptake by inducing the release of adenosine (Tang et al, 2003). Since paeoniflorin has been demonstrated to exhibit so much pharmacological effects, the understanding of pharmacokinetics of paeoniflorin is useful for designing and ideal dosing regimen in pharmacological studies.…”