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Inhibitory adenosine A1-receptors on rat locus coeruleus neurones

An intracellular electrophysiological study

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Summary

Intracellular recordings were performed in α1-pontine slice preparation of the rat brain containing the locus coeruleus (LC). Adenosine (100, 300 μmol/l) and its structural analogues, namely (−)-N6-(R-phenyliso-propyl)-adenosine (R-PIA; 3 – 30 μmol/l) and S-PIA (10, 30 μmol/l), as well as 5′-N-ethylcarboxamido-adenosine (NECA; 3–30 μmol/l) inhibited the firing rate of spontaneous action potentials and produced hyperpolarization; their rank order of potency was RPIA - NECA > S-PIA > adenosine. When applied by superfusion, all agonists strongly desensitized the LC cells; the hyperpolarization never surmounted 6 mV. Upon pressure ejection of adenosine 10 mmol/l from α1- micropipette positioned close to an LC neurone, the membrane potential was raised by 14 mV and the apparent input resistance decreased by 20%. When the membrane potential was hyperpolarized by current injection to α1- similar extent as adenosine did, the fall in input resistance was only 7%. The adenosine uptake inhibitor S-(p-nitrobenzyl)-6-thioguanosine (NBTG) 30 μmol/l decreased the frequency of action potentials alone; on simultaneous bath-application with adenosine 300 μmol/l it potentiated the hyperpolarization caused by the purine derivative. 8-Cyclopentyl-1,3-dipropylxanthine (CPDPX) 0.1 μmol/l had no effect on its own, but it antagonized both R-PIA 30 μmol/l and NBTG 30 μmol/l. A higher concentration of CPDPX (1 μmol/l) facilitated the spontaneous firing. In conclusion, both exogenous and endogenous adenosine activates somatic and/or dendritic A1-receptors of LC neurones leading to an enhancement of potassium conductance and thereby to α1- decreased firing rate and α1- hyperpolarization.

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  1. Department of Pharmacology, University of Freiburg, Hermann-Herder-Strasse 5, D-7800, Freiburg, Federal Republic of Germany

    J. T. Regenold & P. Illes

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  1. J. T. Regenold
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  2. P. Illes
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Regenold, J.T., Illes, P. Inhibitory adenosine A1-receptors on rat locus coeruleus neurones. Naunyn-Schmiedeberg's Arch Pharmacol 341, 225–231 (1990). https://doi.org/10.1007/BF00169735

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