Effects of saw palmetto extract on micturition reflex of rats and its autonomic receptor binding activity.

PURPOSE: We examined the effects of saw palmetto extract (SPE) on the rat micturition reflex and on autonomic receptors in the lower urinary tract. MATERIALS AND METHODS: The effect of SPE was examined on cystometrograms of anesthetized rats induced by intravesical infusion of saline or 0.1% acetic acid. SHR/NDmc-cp (cp/cp) rats received repeat oral administration of SPE and nighttime urodynamic function was determined. The autonomic receptor binding activity of SPE in the rat bladder and prostate was examined by radioligand binding assay. RESULTS: Intraduodenal administration of SPE (60 mg/kg) in anesthetized rat cystometry caused a significant increase in the micturition interval, micturition volume and bladder capacity during intravesical saline infusion. Also, similar administration of SPE at doses of 12 and 20 mg/kg significantly reversed the shortened micturition interval as well as the decreased micturition volume and bladder capacity due to 0.1% acetic acid infusion in a dose dependent manner. In conscious SHR/NDmc-cp (cp/cp) rats repeat oral administration of SPE (6 mg/kg daily) constantly increased the micturition interval and concomitantly decreased voiding frequency. SPE inhibited specific binding of [H]NMS ([N-methyl-H]scopolamine methyl chloride) (bladder) and [H]prazosin (prostate) with IC50 values of 46.1 and 183 microg/ml, respectively. CONCLUSIONS: SPE significantly alleviates urodynamic symptoms in hyperactive rat bladders by increasing bladder capacity and subsequently prolonging the micturition interval. Our data may support the clinical efficacy of SPE for the treatment of lower urinary tract symptoms.

Visual detection of transport-P in peptidergic neurones.

1. Hypothalamic peptidergic neurones possess an uptake process for amines (transport-P), for which prazosin is a substrate. It is characterized by a paradoxical increase in the accumulation of [3H]-prazosin when the concentration of unlabelled prazosin is increased above 10(-7) M. This increase is due to activation of a proton-dependent, vacuolar-type ATPase-linked pump that is blocked by tricyclic antidepressants. This study utilized a fluorescence method to detect amine uptake in individual cells. 2. Prazosin is fluorescent but most of its emission spectrum is in the ultraviolet range. We therefore used an analogue of prazosin in which the furan ring had been substituted with a fluorescent group, BODIPY FL. This compound's emission maximum is in the green part of the visible spectrum. 3. BODIPY FL prazosin accumulated in immortalised peptidergic neurones and the characteristic emission spectrum of the compound was evident in these cells. Accumulation of BODIPY FL prazosin was saturable and was inhibited by the tricyclic antidepressant desipramine and by unlabelled prazosin. As previously described for prazosin, uptake of BODIPY FL prazosin was blocked by cold temperature and by the organic base chloroquine. Thus, prazosin and BODIPY FL prazosin were accumulated by the same uptake process. 4. BODIPY FL prazosin accumulated in a granular distribution, which is compatible with storage in intracellular vesicles. 5. Hypothalamic cells from foetal rats in primary culture also accumulated BODIPY FL prazosin by a desipramine-sensitive process. Uptake was predominantly in neurones and glial cells did not accumulate the amine. 6. Fluorescent detection provides visual evidence for amine uptake in peptidergic neurones and should enable detailed study of the distribution of this process in the brain.

In vitro inhibitory effects of chebulinic acid on the contractile responses of cardiovascular muscles.

1. The effects of chebulinic acid, which has been shown to elicit blood pressure lowering effect in rats, on aortic vascular contraction as well as cardiac contraction were studied in rats. 2. Chebulinic acid had no effect on KCl-induced aortic contraction, but irreversibly inhibited the contractile responses to phenylephrine in an apparently non-competitive manner. Chebulinic acid also inhibited contractile responses of rat aorta to 5-hydroxytryptamine and angiotensin II. 3. Chebulinic acid inhibited the binding of [3H]-prazosin to dog aortic microsomal membranes in a concentration-dependent manner with an IC50 value of 0.34 mmol/L. Results of saturation binding experiments suggest a mixed mode of inhibition by chebulinic acid (i.e. a decrease in both the maximal number of binding sites and the affinity for prazosin). 4. Chebulinic acid concentration-dependently and reversibly inhibited the maximal left ventricular pressure of rat heart in a Langendorff preparation with 50% inhibition occurring at a concentration of 0.3 nmol/L. 5. We conclude that chebulinic acid exerts non-specific inhibitory actions in vascular preparations. Its inhibitory effect on cardiac contraction was reversible and three orders of magnitude more potent than that on vascular contraction. We suggest that the hypotensive effect of chebulinic acid is probably mediated via the decrease in cardiac output resulting from reduced left ventricular contraction.

Tetrandrine, a calcium antagonist of Chinese herbal origin, interacts with vascular muscle alpha 1-adrenoceptor.

The effects of tetrandrine (TET) on the contractile responses of rat aortic rings and perfused rat mesenteric arteries to phenylephrine (PE) were investigated. TET inhibited the maximal contraction to PE in a concentration-dependent manner. TET significantly inhibited the transient contraction in Ca(2+)-free medium presumably due to release of intracellular Ca2+ after activation of alpha 1-adrenoceptors. However, it caused a stronger inhibition of the sustained contraction in Ca(2+)-containing medium presumably the result of Ca2+ influx. TET has no inhibitory effect on caffeine-induced transient contraction. Radioligand receptor binding study using isolated dog aortic muscle membranes indicated that TET inhibited the binding of 3H-prazosin in a competitive manner, hence showing that TET interacted directly with the alpha 1-adrenoceptors. Thus, TET affected PE-induced aortic contractions by multiple mechanisms, inhibiting interaction of PE with alpha 1-adrenoceptors and interfering with PE-induced responses involving both Ca2+ entry and release.

Noradrenergic regulation of cytosol estrogen receptors in female rat hypothalamus: possible role of alpha 2-noradrenergic receptors.

Because of the previous work demonstrating that the alpha 1-noradrenergic receptor antagonist, prazosin, decreases the concentration of cytosol estrogen receptors in rat mediobasal hypothalamus, a series of experiments was performed to determine the specificity of this effect to the alpha 1-noradrenergic system. Injection of the alpha 2-noradrenergic antagonist, yohimbine, caused a decrease in the concentration of estrogen receptors in mediobasal hypothalamus. In addition, the down-regulation of cytosol estrogen receptors by either the alpha 1-noradrenergic antagonist, prazosin, or the alpha 2-noradrenergic antagonist, yohimbine, could be blocked by pretreatment with the alpha 2-noradrenergic agonist, clonidine. The alpha 1-noradrenergic agonist, phenylephrine, was ineffective in blocking the effects of the alpha 1-noradrenergic antagonist, prazosin. These results add further support to the hypothesis that the alpha-noradrenergic system modulates the concentration of cytosol estrogen receptors in the rat hypothalamus. They suggest that the modulation may occur by way of alpha 2-noradrenergic receptors in addition to, or instead of, alpha 1-noradrenergic receptors.