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.
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis*; D004088:Dihydroergotoxine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000008:administration & dosage / Q000494:pharmacology; D010869:Pindolol / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004088:Dihydroergotoxine; D010869:Pindolol; D000242:Cyclic AMP; D000241:Adenosine; D007545:Isoproterenol; D004298:Dopamine; D009638:Norepinephrine; D010646:Phentolamine