title: Adenosine reduces GABAergic IPSC frequency via presynaptic A₁ receptors in hypothalamic paraventricular neurons projecting to rostral ventrolateral medulla.
abstract: Adenosine is an inhibitory modulator of neuronal transmission, including GABAergic transmission in the hypothalamus. It is known that the local GABAergic inputs tonically inhibit the hypothalamic paraventricular neurons projecting to the rostral ventrolateral medulla (RVLM; PVN-RVLM neurons) which regulate sympathetic outflow. In this study, we examined the effects of adenosine on GABAergic synaptic transmission in the PVN-RVLM neurons using whole cell patch-clamp combined with the retrograde labeling technique. Adenosine (100 μM) reversibly decreased the frequency of miniature IPSCs (from 3.41 ± 0.75 to 2.19 ± 0.49 Hz) in a concentration-dependent manner (IC₅₀ = 1.0 μM) without affecting the amplitude and the decay time constant of miniature IPSCs. Adenosine increased the paired-pulse ratio of evoked IPSCs from 1.19 ± 0.05 to 2.28 ± 0.09 (P<0.001). The effects of adenosine was mimicked by a selective A₁ receptor agonist (CHA, 10 μM), and blocked by a selective A₁ receptor antagonist (DPCPX, 2 μM), but not by a selective A₂ receptor antagonist (DMPX, 10 μM). In conclusion, the results showed that adenosine inhibits synaptic GABA release via presynaptic A₁ receptors in the PVN-RVLM neurons, indicating a potential of adenosine A₁ receptors in regulating sympathetic tone in normal and disease states.
authors.affiliation: Laboratory of Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Tae Hee
authors.initials: TH
authors.lastname: Han
authors.forename: Soo Hwa
authors.initials: SH
authors.lastname: Jang
authors.forename: So Yeong
authors.initials: SY
authors.lastname: Lee
authors.forename: Pan Dong
authors.initials: PD
authors.lastname: Ryu
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001703:Biophysics; D004558:Electric Stimulation; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D043682:Receptor, Adenosine A1; D014970:Xanthines; C027513:N(6)-cyclohexyladenosine; D005680:gamma-Aminobutyric Acid; C057837:3,7-dimethyl-1-propargylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D013805:Theobromine