Vasoactive intestinal peptide and noradrenaline exert long-term control on glycogen levels in astrocytes: blockade by protein synthesis inhibition.
Vasoactive intestinal peptide (VIP) and noradrenaline (NA) have been previously shown to promote glycogenolysis in mouse cerebral cortex (Magistretti, 1990). This action, which is fully expressed within a few minutes, is exerted on astrocytes (Sorg and Magistretti, 1991). In the present article, we report a second, temporally delayed, action of VIP or NA in primary cultures of mouse cerebral cortical astrocytes; thus, following glycogenolysis, an induction of glycogen resynthesis is observed, resulting, within 9 hr, in glycogen levels that are 6-10 times higher than those measured before the application of either neurotransmitter. This effect of VIP or NA is concentration dependent and, for NA, is mediated by adrenergic receptors of the beta subtype. The continued presence of the neurotransmitter is not necessary for this long-term effect, since pulses as short as 1 min result in the doubling of glycogen levels 9 hr later. The induction of glycogen resynthesis triggered by VIP or NA is dependent on protein synthesis, since both cycloheximide and actinomycin D abolish it entirely. The ability to elicit glycogenolysis is not sufficient per se to trigger the induction of glycogen resynthesis. Thus, two glycogenolytic agents such as methoxamine, an alpha 1-adrenergic agonist, and phorbol 12,13-dibutyrate, both acting via protein kinase C activation, are unable to induce glycogen resynthesis. This observation, taken together with the fact that dibutyryl-cAMP application also results in enhanced glycogen resynthesis, strongly suggests that the long-term effect of VIP or NA is mediated by the cAMP second-messenger pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
Sorg
O
O
Institut de Physiologie, Université de Lausanne, Switzerland.
Magistretti
P J
PJ
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006003:Glycogen / Q000096:biosynthesis / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008729:Methoxamine / Q000494:pharmacology; D051379:Mice; D008959:Models, Neurological; D009638:Norepinephrine / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D007328:Insulin; D014660:Vasoactive Intestinal Peptide; D015240:Phorbol 12,13-Dibutyrate; D003994:Bucladesine; D006003:Glycogen; D003513:Cycloheximide; D008729:Methoxamine; D007545:Isoproterenol; D009638:Norepinephrine