title: Both Astrocytes and Neurons Contribute to the Potentiation Mediated by alpha1-Adrenoceptors of the beta-Adrenergic-Stimulated Cyclic AMP Production in Brain.
abstract: Using primary neuronal or astrocyte cultures from the striatum of the embryonic mouse, we have observed that the beta-adrenergic agonist isoprenaline (10-5 M) induced a more pronounced accumulation of cAMP in astrocytes than in neurons. In both cell types, the alpha-adrenergic selective agonist methoxamine (10-4 M), which alone did not affect the production of cAMP, potentiated the isoprenaline-evoked response. In support of these observations, when associated alpha2-noradrenergic and D1-dopaminergic responses were prevented, the mixed alpha1- and beta-adrenergic agonist noradrenaline (10-5 M) induced a production of cAMP which was totally blocked by propranolol (10-6 M) and partially abolished by prazosin (10-6 M). Since experiments were made in the presence of 3-isobutyl-1-methylxanthine (1 mM), the observed effects of cAMP accumulation were not related to a modulation of phosphodiesterase activities. In addition, both in astrocytes and in neurons, the potentiation by alpha1-adrenergic agonists of the beta-adrenergic-evoked response required external calcium. Using INDo 1 as a fluorescent probe, methoxamine (25 microM) was shown to induce in astrocytes an increase in cytosolic calcium concentration which was prolonged by isoprenaline (10-5 M) only in the presence of external calcium. These results suggest that the prolonged increase in cytosolic calcium concentration linked to the activation of alpha1- and beta-adrenergic receptors is responsible for the potentiation of the beta-adrenergic-induced production of cAMP, which is partially dependent on external calcium.
authors.affiliation: College de France-INSERM U114, Chaire de Neuropharmacologie, 11 Place Marcelin Berthelot, 75231 Paris Cedex 05, France.
authors.forename: P.
authors.initials: P
authors.lastname: Marin
authors.forename: J. C.
authors.initials: JC
authors.lastname: Delumeau
authors.forename: J.
authors.initials: J
authors.lastname: Cordier
authors.forename: J.
authors.initials: J
authors.lastname: Glowinski
authors.forename: J.
authors.initials: J
authors.lastname: Premont