Synergistic regulation of cytosolic Ca2+ concentration by somatostatin and alpha 1-adrenergic agonists in mouse astrocytes.
The effects of somatostatin and alpha 1-adrenergic receptor agonists on cytosolic Ca2+ in striatal astrocytes from the embryonic mouse in primary culture have been investigated by microfluorimetry. Methoxamine or somatostatin induced a transitory increase in cytosolic Ca2+, but their combined addition led to a sustained increase in cytosolic Ca2+ which seems to be due to a Ca2+ influx since it was not observed in the absence of external Ca2+. Voltage-independent Ca2+ channels contribute to this process. Indeed, voltage-operated calcium channels are not involved since neither dihydropyridines nor La3+ were effective in suppressing the sustained cytosolic Ca2+ elevation. Moreover, depolarization by 50 mM KCl, which was ineffective alone, suppressed the effect of somatostatin observed in the presence of the alpha 1 agonist, methoxamine. The implication of arachidonic acid in the observed potentiation is suggested by the following observations: 1) arachidonic acid induced a sustained elevation of cytosolic Ca2+ similar to that evoked by the co-application of methoxamine and somatostatin; 2) the addition of ETYA, an inactive and non-metabolizable analogue of arachidonic acid suppressed the calcium plateau produced by the agonists. In addition, direct activation of PKC by an exogeneous diacylglycerol analogue allowed somatostatin alone to evoke a sustained elevation of cytosolic Ca2+. Therefore, methoxamine through the successive activation of PLC and PKC could allow a lipase, probably PLA2, to be stimulated by somatostatin. Since arachidonic acid has already been shown to trigger the opening of K+ channels and the formation of inositol phosphates, somatostatin, through the arachidonic acid-mediated hyperpolarization could increase the Ca2+ driving force and thus improve Ca2+ influx through the inositol phosphate gated channels.
Delumeau
J C
JC
Laboratoire de Neuropharmacologie INSERM, Paris, France.
Marin
P
P
Tence
M
M
Cordier
J
J
Glowinski
J
J
Premont
J
J
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism*; D004357:Drug Synergism; D004789:Enzyme Activation; D008729:Methoxamine / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009994:Osmolar Concentration; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D013004:Somatostatin; D011493:Protein Kinase C; D008729:Methoxamine; D002118:Calcium