Effect of adrenergic agonists on glycogenolysis in primary cultures of astrocytes.
A stimulation of glycogenolysis in astrocytes by adrenergic agonists has repeatedly been demonstrated in the literature. However, some confusion exists regarding which type of adrenergic receptor subtype is involved, and little information is available about rates of glycogenolysis and potencies of adrenergic agonists. In the present study, we have investigated these parameters using primary cultures of mouse astrocytes which constitute a reliable model for their in vivo counterparts. Antagonists as well as agonist studies revealed that noradrenaline acts both on a beta- and on an alpha 2-receptor. Isoproterenol and clonidine, agonists acting relatively specifically on only one of these receptor subtypes could, on their own, stimulate glycogenolysis and the effect by noradrenaline could be inhibited by alprenolol (beta-adrenergic antagonist) and/or yohimbine (alpha 2-adrenergic antagonist) but not by prazosin (alpha 1-adrenergic antagonist). Excess potassium also stimulated glycogenolysis but this effect was not antagonized by adrenergic antagonists, alone or in combination. The involvement of an alpha 2-adrenergic receptor in a homogeneous culture of astrocytes provides proof that not all alpha 2-adrenergic receptors in brain are presynaptic. The maximum rate of stimulated glycogenolysis was calculated to be 3-7 nmol/min per mg protein. Computer analysis showed that the EC50 values for noradrenaline, isoproterenol and clonidine were 4.6 x 10(-8) M, 3.0 x 10(-7) M, and 6.5 x 10(-7) M, respectively.
Subbarao
K V
KV
Department of Pharmacology, University of Saskatchewan, Saskatoon, Canada.
Hertz
L
L
D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003000:Clonidine / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D015016:Yohimbine; D000526:Alprenolol; D006003:Glycogen; D007545:Isoproterenol; D003000:Clonidine; D011188:Potassium; D009638:Norepinephrine; D011224:Prazosin