Further Elucidation of a Pertussis Toxin-Sensitive Transmembrane Signaling Mechanism Involved in Central...

In adult male Sprague-Dawley rats anesthetized with pentobarbital sodium, we elucidated the molecular consequence of central alpha(2)-adrenoceptor activation. The hypotensive and negative chronotropic and inotropic actions of the alpha(2)-adrenoceptor agonist guanabenz were used as our experimental index. Intracerebroventricular administration of pertussis toxin (2.5 &mgr;g) significantly attenuated the cardiovascular suppressant effects of the aminoguanidine compound (100 &mgr;g/kg i.v.). However, application of N-ethylmaleimide (0.125 or 0.250 &mgr;g), phorbol 12-myristate 13-acetate (1.25 or 2.50 &mgr;g), cholera toxin (1.25 or 2.50 &mgr;g) or forskolin (12.5 or 25.0 &mgr;g) 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 &mgr;g), N-ethylmaleimide (0.0125 or 0.05 &mgr;g), phorbol 12-myristate 13-acetate (0.125 or 0.25 &mgr;g), cholera toxin (0.125 or 0.25 &mgr;g) or forskolin (1.25 or 2.50 &mgr;g) 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 alpha(2)-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. Copyright 1994 S. Karger AG, Basel