| Description: |
Pteropodine acts as a positive modulator of muscarinic M(1) and 5-HT(2) receptors. Pteropodine shows antigenotoxic, antioxidant and lymphocyte induction effects, it also shows strong apoptotic effect on acute leukaemic lymphoblasts. |
| Targets: |
Calcium Channel | 5-HT Receptor | Bcl-2/Bax |
| In vitro: |
| Eur J Pharmacol. 2002 May 24;444(1-2):39-45. | | Pteropodine and isopteropodine positively modulate the function of rat muscarinic M(1) and 5-HT(2) receptors expressed in Xenopus oocyte.[Pubmed: 12191580] | Pteropodine and isoPteropodine are heteroyohimbine-type oxindole alkaloid components of Uncaria tomentosa (Willd.) DC, a Peruvian medicinal plant known as cat's claw.
METHODS AND RESULTS:
In this study, the effects of these alkaloids on the function of Ca(2+)-activated Cl(-) currents evoked by stimulation of G protein-coupled muscarinic M(1) acetylcholine and 5-HT(2) receptors were studied in Xenopus oocytes in which rat cortex total RNA was translated. Pteropodine and isoPteropodine (1-30 microM) failed to induce membrane current by themselves. However, these alkaloids markedly enhanced the current responses evoked by both acetylcholine and 5-hydroxyhyptamine (5-HT) in a concentration-dependent and reversible manner with the maximal effects at 30 microM. Pteropodine and isoPteropodine produced 2.7- and 3.3-fold increases in the acetylcholine response with EC(50) values of 9.52 and 9.92 microM, respectively, and 2.4- and 2.5-fold increases in the 5-HT response with EC(50) values of 13.5 and 14.5 microM, respectively. In contrast, in oocytes injected with total RNA from the rat cerebellum or spinal cord, neither alkaloid had an effect on the metabotropic current responses mediated by glutamate receptor(1 and 5) (mGlu(1/5)) receptors or ionotropic responses mediated by N-methyl-D-aspartate, kainic acid or glycine. Pteropodine and isoPteropodine (10 microM) significantly reduced the EC(50) values of acetylcholine and 5-HT that elicited current responses, but had no effect on the maximal current responses elicited by acetylcholine and 5-HT. On the other hand, mitraphylline, a stereoisomer of Pteropodine, failed to modulate acetylcholine- and 5-HT-induced responses.
CONCLUSIONS:
These results suggest that Pteropodine and isoPteropodine act as positive modulators of muscarinic M(1) and 5-HT(2) receptors. |
|
| In vivo: |
| J Biomed Biotechnol. 2005;2005(3):242-7. | | Genotoxic and cytotoxic studies of beta-sitosterol and pteropodine in mouse.[Pubmed: 16192682 ] | Beta-sitosterol (BS) and Pteropodine (PT) are constituents of various plants with pharmacological activities potentially useful to man. The chemicals themselves possess biomedical properties related to the modulation of the immune and the nervous systems, as well as to the inflammatory process. Therefore, safety evaluation of the compounds is necessary in regard to their probable beneficial use in human health.
METHODS AND RESULTS:
The present study evaluates their genotoxic and cytotoxic potential by determining the capacity of the compounds to induce sister chromatid exchanges (SCE), or to alter cellular proliferation kinetics (CPK) and the mitotic index (MI) in mouse bone marrow cells. Besides, it also determines their capacity to increase the rate of micronucleated polychromatic erythrocytes (MNPE) in peripheral mouse blood, and the relationship polychromatic erythrocytes/normochromatic erythrocytes (PE/NE) as an index of cytotoxicity. For the first assay, four doses of each compound were tested: 200, 400, 600, and 1000 mg/kg in case of BS, and 100, 200, 300, and 600 mg/kg for PT. The results in regard to both agents showed no SCE increase induced by any of the tested doses, as well as no alteration in the CPK, or in the MI. With respect to the second assay, the results obtained with the two agents were also negative for both the MNPE and the PE/NE index along the daily evaluation made for four days.
CONCLUSIONS:
In the present study, the highest tested dose corresponded to 80% of the LD(50) obtained for BS and to 78% in the case of PT. The results obtained establish that the studied agents have neither genotoxic nor cytotoxic effect on the model used, and therefore they encourage studies on their pharmacological properties. |
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