GABA heteroreceptors modulate noradrenaline release in human dental pulp.
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 [(3)H]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 [(3)H]NA at S2 with that at S1 in the presence and absence of the compound. Baclofen (3 µM) inhibited the release of [(3)H]NA (IC50 = 2 µM), an action reversed by Sch 50911 (10 µM). GABA (100 µM) inhibited the release of [(3)H]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.
School of Dentistry, The University of Adelaide, Adelaide, South Australia, 5005, Australia.
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DA
Parker
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V
Marino
D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D003782:Dental Pulp / Q000294:innervation / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D006801:Humans; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects; D013566:Sympathomimetics / Q000378:metabolism*; D013997:Time Factors; D046509:Tissue Culture Techniques; D014316:Tritium; D055815:Young Adult
D001418:Baclofen; D001640:Bicuculline; D018118:Chloride Channels; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009025:Morpholines; D009638:Norepinephrine; D010852:Picrotoxin; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D017661:Receptors, Presynaptic; D013566:Sympathomimetics; D014316:Tritium; C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid
Cl- channel inhibitor; GABAA/B receptors; baclofen; bicuculline; sympathetic nervous system; γ-aminobutyric acid