2-3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline and 6-fluoronorepinephrine

The inhibitory activity in the cerebellar network, as investigated in acute brain slices from 14-20 days old rats, is modulated by alpha1-adrenergic stimulation. The specific alpha1-adrenoceptor agonist phenylephrine (PhE; 10 microM) or the alpha-adrenoceptor agonist 6-fluoronoradrenaline (10 microM) increases the frequency and the amplitude of spontaneous postsynaptic currents (sPSC) in Purkinje neurons. The effects are sensitive to the alpha1-adrenoceptor antagonists prazosin (30 microM) and phentolamine (10 microM). The PhE-induced augmentation is suppressed when phospholipase C is blocked by preincubation with U73122 (10 microM) but is not affected by inhibition of protein kinases with H7 (10 microM) or GF109203X (10 microM). Involvement of intracellular Ca(2+) stores was shown by a reduced PhE effect after blocking of SERCA pumps with cyclopiazonic acid (30 microM) and thapsigargin (1 microM). The persistence of the PhE effect on the frequency of miniature postsynaptic currents, as recorded in presence of tetrodotoxin, indicates a presynaptic localization of the alpha1-adrenoceptors. A block of voltage-gated Ca(2+) channels with nifedipine, verapamil, or omega-conotoxin MVIIC did not suppress the PhE-induced increase of the frequency and amplitude of sPSC. The results suggest that alpha1-adrenoceptors at presynaptic terminals mediate an increase of the spontaneous synaptic inhibition of Purkinje neurons in the cerebellar cortex via release of Ca(2+) from intracellular stores.

Topics: 2-Amino-5-phosphonovalerate; Adenosine Triphosphate; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Adrenergic beta-Agonists; Animals; Animals, Newborn; Cerebellum; Drug Interactions; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; GABA Antagonists; In Vitro Techniques; Isoproterenol; Membrane Potentials; Norepinephrine; Patch-Clamp Techniques; Phentolamine; Phenylephrine; Picrotoxin; Prazosin; Purkinje Cells; Quinoxalines; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-1; Synapses; Tetrodotoxin; Time Factors