Accumulations of cyclic AMP in adenine-labeled cell-free preparations from guinea pig cerebral cortex: role of alpha-adrenergic and H1-histaminergic receptors.
Norepinephrine, histamine, adenosine, glutamate, and depolarizing agents elicit accumulations of radioactive cyclic AMP from adenine-labeled nucleotides in particulate fractions from Krebs-Ringer homogenates of guinea pig cerebral cortex. The particulate fractions contain sac-like entities, which apparently are associated with a significant portion of the membranal adenylate cyclase. Particulate fractions from sucrose homogenates are a less effective source of such responsive entities. Activation of the adenine-labeled cyclic AMP-generating systems by norepinephrine is by means of alpha-adrenergic receptors, while activation by histamine is through H1- and H2-histaminergic receptors. Adenosine responses are potentiated by the amines and are antagonized by alkylxanthines. Glutamate and depolarizing agents appear to elicit accumulations of cyclic AMP via "release" of endogenous adenosine. It is proposed, based on the virtual absence of an alpha-adrenergic or H1-histaminergic response in the presence of a combination of potent adenosine and H2-histaminergic antagonists, that alpha-adrenergic and H1-histaminergic receptor mechanisms do not activate adenylate cyclase directly in brain slices or Krebs-Ringer particulate fractions, but merely facilitate activation by beta-adrenergic, H2-histaminergic, or adenosine receptors.
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002474:Cell-Free System; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000242:Cyclic AMP / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D008785:Metiamide / Q000494:pharmacology; D008854:Microscopy, Electron; D009638:Norepinephrine / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011968:Receptors, Histamine / Q000502:physiology*; D011969:Receptors, Histamine H1 / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D005971:Glutamates; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D008785:Metiamide; D006632:Histamine; D013806:Theophylline; D000242:Cyclic AMP; C028322:8-phenyltheophylline; D000241:Adenosine; D009638:Norepinephrine