Increased sensitivity to injected 5′-guanylylimidodiphosphate of the sodium efflux in barnacle muscle fibres preexposed to aldosterone

Abstract

1. A study has been made of the response to injected Gpp(NH)p of the ouabain-insensitive Na efflux in barnacle muscle fibres preexposcd to aldosterone. 2. The response to injected Gpp(NH)p is not only greater in size than in unexposed fibres but also sustained. 3. Injection of MgCl 2 following peak stimulation causes a partial reversal of the response. 4. Injection of ATPNa 2 (and 5′-App(NH(p) leads to a sustained stimulatory response which is not significantly greater than that seen in unexposed fibres. 5. MgCl 2 injection causes complete reversal of this response. 6. The response of preexposed fibres to injected CaCl 2 in varying concentration and to injected cholera toxin is not significantly different from that seen in unexposed fibres. 7. This is also true of Gpp(NH)p when it is injected after peak stimulation by cholera toxin. 8. Prior application of verapamil (10 −4 M) drastically reduces the response to injected Gpp(NH)p. 9. The residual response is sustained but markedly reduced by injected Mg 2+. Fe or Zn. 10. Injection of PKI following Gpp(NH)p reduces the response, provided PK.I is also injected before Gpp(NH)p. By contrast, injection of R ll subunits causes a partial reversal if injected only once. 11. Imipramine and trifluoperazine. when applied externally (5 × 10 −5 M), cause almost complete reversal of the response. 12. The suggestion is made that the response to injected Gpp(NH)p is mainly due to activation of Ca 2+ -channels resulting in activation of the calmodulin/Ca-dependent form of adenylate cyclase and that the primary site of aldosterone action is at the level of the calmodulin form of adenylate cyclase.