Effect of dihydroergotoxine on cyclic-AMP-generating systems in rat cerebral cortex slices.

In slices of rat cerebral cortex, cyclic-AMP formation is stimulated in response to added noradrenaline (NA), isoproterenol (ISP) or adenosine. The effect of ISP could be antagonized only by the selective beta-adrenoceptor-blocking agent pindolol, whereas the stimulating effect of NA could be antagonized by both alpha- and beta-adrenoceptor-blocking agents. Dihydroergotoxine (DHET) at low concentrations (10(-8)M) antagonized the stimulating effect of NA but not of ISP or adenosine, suggesting that this substance has a high affinity for central alpha-adrenoceptors. We could also show that DHET is accumulated in rat cerebral cortex after repeated oral application. In slices of cortex obtained from rats after treatment with DHET for 3 and 6 weeks, but not after 1 week, NA had a significant lower effect on cyclic-AMP formation than in slices from corresponding controls.