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

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Abstract
Using primary neuronal or astrocyte cultures from the striatum of the embryonic mouse, we have observed 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 .alpha.2-noradrenergic and D1-dopaminergic responses were prevented, the mixed .alpha.1- 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 on cAMP accumulation were not related to a modulation of phosphodiesterase activities. In addition, both in astrocytes and in neurons, the potentiation by .alpha.1-adrenergic agonists of the .beta.-adrenergic-evoked response required external calcium. Using INDO 1 as a fluorescent probe, methoxamine (25 .mu.M) 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 .alpha.1- and .beta.-adrenergic receptors is responsible for the potentiation of the .beta.-adrenergic-induced production of cAMP, which is partially dependent on external calcium.