Inhibitory adenosine A1-receptors on rat locus coeruleus neurones. An intracellular electrophysiological study.
Intracellular recordings were performed in a pontine slice preparation of the rat brain containing the locus coeruleus (LC). Adenosine (100, 300 mumol/l) and its structural analogues, namely (-)-N6-(R-phenylisopropyl)-adenosine (R-PIA; 3-30 mumol/l) and S-PIA (10, 30 mumol/l), as well as 5'-N-ethylcarboxamido-adenosine (NECA; 3-30 mumol/l) inhibited the firing rate of spontaneous action potentials and produced hyperpolarization; their rank order of potency was R-PIA congruent to NECA greater than S-PIA greater than 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 a 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 a similar extent as adenosine did, the fall in input resistance was only 7%. The adenosine uptake inhibitor S-(p-nitrobenzyl)-6-thioguanosine (NBTG) 30 mumol/l decreased the frequency of action potentials alone; on simultaneous bath-application with adenosine 300 mumol/l it potentiated the hyperpolarization caused by the purine derivative. 8-Cyclopentyl-1,3-dipropylxanthine (CPDPX) 0.1 mumol/l had no effect on its own, but it antagonized both R-PIA 30 mumol/l and NBTG 30 mumol/l. A higher concentration of CPDPX (1 mumol/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 a decreased firing rate and a hyperpolarization.
Regenold
J T
JT
Department of Pharmacology, University of Freiburg, Federal Republic of Germany.
Illes
P
P
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D004594:Electrophysiology; D006151:Guanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000378:metabolism*; D013872:Thionucleosides / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D011983:Receptors, Purinergic; D013872:Thionucleosides; D014970:Xanthines; D006151:Guanosine; C002121:6-(4-nitrobenzylthio)guanosine; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine