Both Astrocytes and Neurons Contribute to the Potentiation Mediated by α1‐Adrenoceptors of the β‐Adrenergic‐Stimulated Cyclic AMP Production in Brain

The 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.

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.