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Further elucidation of a pertussis toxin-sensitive transmembrane signaling mechanism involved in central α2-adrenoceptor activation in the rat

  • Original Paper
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Journal of Biomedical Science

Abstract

In adult male Sprague-Dawley rats anesthetized with pentobarbital sodium, we elucidated the molecular consequence of central α2-adrenoceptor activation. The hypotensive and negative chronotropic and inotropic actions of the α2-adrenoceptor agonist guanabenz were used as our experimental index. Intracerebroventricular administration of pertussis toxin (2.5 µg) significantly attenuated the cardiovascular suppressant effects of the aminoguanidine compound (100 µg/kg i.v.). However, application of N-ethylmaleimide (0.125 or 0.250 µg), phorbol 12-myristate 13-acetate (1.25 or 2.50 µg), cholera toxin (1.25 or 2.50 µg) or forskolin (12.5 or 25.0 µg) into the lateral cerebral ventricle elicited no appreciable blunting effect on the circulatory depression produced by guanabenz. These results were essentially duplicated when pertussis toxin (0.125 or 0.250 µg), N-ethylmaleimide (0.0125 or 0.05 µg), phorbol 12-myristate 13-acetate (0.125 or 0.25 µg), cholera toxin (0.125 or 0.25 µg) or forskolin (1.25 or 2.50 µg) was microinjected bilaterally to the nucleus reticularis gigantocellularis, a medullary site believed to be intimately related to the antihypertensive action of guanabenz. These findings suggest that stimulation of the α2-adrenoceptors in the medulla oblongata may result in the activation of a pertussis toxin-sensitive GTP-binding regulatory protein. They further suggest that the biologic signals subsequent to this action may not be linked to Gs, Gi or Gp but possibly Go.

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Authors and Affiliations

  1. Institute of Pharmacology, National Yang-Ming Medical College, 11221, Taipei, Taiwan (ROC)

    C. H. Chen, K. S. Lin & S. H. H. Chan PhD

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  1. C. H. Chen
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  2. K. S. Lin
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  3. S. H. H. Chan PhD
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Chen, C.H., Lin, K.S. & Chan, S.H.H. Further elucidation of a pertussis toxin-sensitive transmembrane signaling mechanism involved in central α2-adrenoceptor activation in the rat. J Biomed Sci 1, 13–18 (1993). https://doi.org/10.1007/BF02258335

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  • DOI: https://doi.org/10.1007/BF02258335

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