Neuropeptides modulate the β-adrenergic response of purified astrocytes in vitro

Abstract

Neuropeptides may have functions in the central nervous system (CNS) other than altering neuronal excitability. For example, they may act as regulators of brain metabolism by affecting glycogenolysis¹. Since it has been suggested that glial cells might provide metabolic support for neuronal activity^2,3, they may well be one of the targets for neuropeptide regulation of metabolism. Consistent with this view are reports that peptidecontaining nerve terminals have been seen apposed to astrocytes^4,5, but it is also quite possible that peptides could act at sites lacking morphological specialization^6,7. Primary cultures containing CNS glial cells have been shown to respond to β-adrenergic agonists with an increase in cyclic AMP and, as a result, with an increase in glycogenolysis^8,9 and have also been shown to respond to a variety of peptides with changes in cyclic AMP^10–12. In the study reported here, we have examined the effects of several peptides on relatively pure cultures of rat astrocytes. We demonstrate that the increase in intracellular cyclic AMP induced by noradrenaline is markedly enhanced by somatostatin and substance P and is inhibited by enkephalin, even though these peptides on their own have little or no effect on the basal levels of cyclic AMP. Vasoactive intestinal peptide ( VIP) on the other hand increases cyclic AMP in the absence of noradrenaline. These results suggest that neuropeptides influence glial cells as well as neurones in the CNS and, in the case of somatostatin and substance P, provide further examples of neuropeptides modulating the response to another chemical signal without having a detectable action on their own.