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 Here we report that VIP induces a concentration-dependent hydrolysis of newly synthesized [3H]glycogen in mouse cortical slices. This effect is independent of and 20 times more potent than the glycogenolytic action of norepinephrine (30), confirmed by us in this study. The presence of two independent transmitters mediating glycogenolytic responses in cerebral cortex, similar to their action in the periphery, may indicate that hormones regulating energy metabolism systemically also may regulate this function within precise anatomical domains ofthe central nervous system.Vasoactive intestinal peptide (VIP) is a 28-amino acid polypeptide first isolated from porcine intestine by Said and Mutt (1). It shares structural homologies with other gastrointestinal peptides, such as glucagon, secretin, and gastric inhibitory peptide (2). Its spectrum of biological activities includes systemic vasodilation, increased cardiac output, and hyperglycemia (1); smooth muscle relaxation (3); some differential effects on secretory processes in the gastrointestinal tract (4-6); and glycogenolysis in liver slices (7). VIP-immunoreactive material has been identified in the nervous system (8-11), the highest concentration being in cerebral cortex (9, 11); neurons with VIPlike immunoreactivity have been visualized in the central nervous system (10-13). In addition to its presence in neurons, other criteria for attributing a possible neurotransmitter function to VIP include its localization in (14) and potassium-induced release from (14, 15) synaptosomal preparations. Furthermore, specific recognition sites for radiolabeled VIP have been demonstrated in rat (16) and guinea pig (17) brain membranes, and a VIP-stimulated adenylate cyclase has been identified in various areas of the central nervous system (18,19).Glycogen is the single largest energy reserve in the brain (20). It can be visualized by light and electron microscopy both MATERIALS AND METHODS Animals. Young adult male Swiss albino mice (18-20g) were used throughout the study. They were housed six per cage and maintained in an alternating light/dark cycle (12:12 hr) with free access to food and water.Tissue Preparation and Incubations. The method described by Quach et al (30) was used: mice were killed by decapitation, the brain quickly was removed, the cerebral cortex was dissected on ice and placed in a modified Krebs-Ringer bicarbonate buffer (120 mM NaCl/5 mM KCV2.6 mM CaCl2/0.67 mM MgSO41.2 mM KH2POJ3 mM glucose/27.5 mM NaHCO3) previously gassed with 02/CO2 (95:5) to maintain pH 7.4. The cortex was then placed, with its ventral surface facing down, on a McIlwain tissue slicer (Mickle Laboratory Engineering, Gomshall, Surrey, England); 250 x 250 Am slices were prepared and resuspended in ice-cold Krebs-Ringer bicarbonate buffer (6 ml per cortex). After replacing the supernatant with fresh medium, the slices were incubated in a shaking water bath at 37C under continuous gassing (02/CO2, 95:...

Selective Excitation of Subtypes of Neocortical Interneurons by Nicotinic Receptors

“…Third, the injection of VIP into the cortex increase the cerebral blood flow (Itakura et al, 1987). Fourth, VIP activates glycogenolysis in neocortical slices (Magistretti et al, 1981). Therefore, the nicotinic excitation of VIPergic interneurons reported in this study may be critical for locally increasing the energy supply in the neocortex during periods of increased neuronal activity.…”

Energy Metabolism in Astrocytes: High Rate of Oxidative Metabolism and Spatiotemporal Dependence on Glycolysis/Glycogenolysis

“…There is accordingly strong in situ evidence to support the hypothesis that glutamate stimulates astrocytic oxidative metabolism of available fuels. Glutamate does not stimulate glycogenolysis in brain slices (Magistretti et al, 1981), and it increases glycogen formation in cultured astrocytes (Swanson et al, 1990). It is not known if in vivo rates of glutamate oxidation change during activation or when activation is stopped or if glycolytic responses to glutamate occur in peripheral astrocytic processes.…”

Glucose-targeted niosomes deliver vasoactive intestinal peptide (VIP) to the brain

“…It exerts diverse peripheral biological functions, such as anti-inflammatory and immunomodulatory effects, regulation of cell growth and differentiation and participation in the development of neural tissue (Muller et al, 1995). It also possesses neuroprotective properties that influence the survival of activity-dependent neurons in the central nervous system, and plays an important role in cerebral metabolism (Magistretti et al, 1981) and in cerebral carcinogenesis (Lelièvre et al, 1998). VIP may have interesting applications in the treatment of various neurological disorders: a lipophilic VIP analogue was proposed as a therapy against Alzheimer's disease (Gozes et al, 1996).…”