GABA Heteroreceptors Modulate Noradrenaline Release in Human Dental Pulp

Abstract

γ-aminobutyric-acid-containing neurons and GABA_B receptors have been identified in human dental pulp; however, their significance in pulpal physiology is unclear. The purpose of this study was to determine whether pre-synaptic GABAergic heteroreceptors influence the release of noradrenaline (NA). Segments of vital pulp were incubated in [³H]NA (0.6 μM) and superfused with Krebs solution. GABA, a GABA_B receptor agonist (baclofen), GABA_{A and B} receptor antagonists [bicuculline and (+)-(S)-5, 5-dimethylmorpholinyl-2-acetic acid (Sch 50911), respectively], and a GABA_A receptor-mediated Cl^- channel inhibitor (picrotoxin) were added to the superfusion medium at least 10 min prior to the second period of stimulation (S₂). Sympathetic nerves were stimulated electrically after 70 (S₁) and 115 (S₂) min. We determined the effects of agonists/antagonists by comparing the overflow of [³H]NA at S₂ with that at S₁ in the presence and absence of the compound. Baclofen (3 µM) inhibited the release of [³H]NA (IC₅₀ = 2 µM), an action reversed by Sch 50911 (10 µM). GABA (100 µM) inhibited the release of [³H]NA (IC₅₀ = 75 µM), an effect reversed by Sch 50911 (10 µM) but not by bicuculline (10 µM). However, picrotoxin (100 µM) prevented the inhibitory action of GABA. GABA_B and GABA_A heteroceptors mediate the release of NA from sympathetic nerves in human dental pulp in vitro.