Vasoactive intestinal polypeptide induces glycogenolysis in mouse cortical slices: a possible regulatory mechanism for the local control of energy metabolism.

Abstract

Mouse cerebral cortex slices will synthesize [3H]glycogen in vitro. Vasoactive intestinal polypeptide (VIP) stimulates the enzymatic breakdown of this [3H]glycogen. The concentration giving 50% of maximum effectiveness (EC50) is 26 nM. Under the same experimental conditions norepinephrine also induces a concentration-dependent [3H]glycogen hydrolysis with an EC50 of 500 nM. The effect of VIP is not mediated by the release of norepinephrine because it is not blocked by the noradrenergic antagonist d-1-propranolol and is still present in mice in which an 85% depletion of norepinephrine was induced by intracisternal 6-hydroxydopamine injections. Other cortical putative neurotransmitters such as GABA, aspartic acid, glutamic acid, somatostatin and acetylcholine (tested with the agonist carbamylcholine) do not induce a breakdown of [3H]glycogen. This glycogenolytic effect of VIP and norepinephrine, presumed to be mediated by cAMP formation, should result at the cellular level in an increased glucose availability for the generation of phosphate-bound energy. Given the narrow radial pattern of arborization of the intracortical VIP neuron and the tangential intracortical trajectory of the noradrenergic fibers, these 2 systems may function in a complementary fashion: VIP regulating energy metabolism locally, within individual columnar modules, and norepinephrine exerting a more global effect that spans adjacent columns.