Presynaptic adenosine A1 receptors regulate retinohypothalamic neurotransmission in the hamster suprachiasmatic nucleus.
Adenosine has been implicated as a modulator of retinohypothalamic neurotransmission in the suprachiasmatic nucleus (SCN), the seat of the light-entrainable circadian clock in mammals. Intracellular recordings were made from SCN neurons in slices of hamster hypothalamus using the in situ whole-cell patch clamp method. A monosynaptic, glutamatergic, excitatory postsynaptic current (EPSC) was evoked by stimulation of the optic nerve. The EPSC was blocked by bath application of the adenosine A(1) receptor agonist cyclohexyladenosine (CHA) in a dose-dependent manner with a half-maximal concentration of 1.7 microM. The block of EPSC amplitude by CHA was antagonized by concurrent application of the adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). The adenosine A(2A) receptor agonist CGS21680 was ineffective in attenuating the EPSC at concentrations up to 50 microM. Trains of four consecutive stimuli at 25 ms intervals usually depressed the EPSC amplitude. However, after application of CHA, consecutive responses displayed facilitation of EPSC amplitude. The induction of facilitation by CHA suggested a presynaptic mechanism of action. After application of CHA, the frequency of spontaneous EPSCs declined substantially, while their amplitude distribution was unchanged or slightly reduced, again suggesting a mainly presynaptic site of action for CHA. Application of glutamate by brief pressure ejection evoked a long-lasting inward current that was unaffected by CHA at concentrations sufficient to reduce the evoked EPSC amplitude substantially (1 to 5 microM), suggesting that postsynaptic glutamate receptor-gated currents were unaffected by the drug. Taken together, these observations indicate that CHA inhibits optic nerve-evoked EPSCs in SCN neurons by a predominantly presynaptic mechanism.
Hallworth
Richard
R
Department of Otolaryngology - Head and Neck Surgery, University of Texas Health Science Center at San Antonio, 78229-3900, USA.
Cato
Matthew
M
Colbert
Costa
C
Rea
Michael A
MA
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D008647:Mesocricetus; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D010627:Phenethylamines / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D017661:Receptors, Presynaptic / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D012160:Retina / Q000166:cytology* / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000166:cytology* / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D014795:Visual Pathways / Q000166:cytology / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology
D000959:Antihypertensive Agents; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D017661:Receptors, Presynaptic; D018047:Receptors, Purinergic P1; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C027513:N(6)-cyclohexyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine