Uptake and release of [(3)H]GABA in human dental pulp.
The purpose of this study was to determine whether (a) an uptake system for gamma-aminobutyric acid (GABA) exists in human dental pulp, (b) GABA can be released from nerves in this tissue, and (c) GABA(B) autoreceptors modulate release of this transmitter. Segments of vital pulp were incubated in [(3)H]GABA (0.1-10 microM) for up to 120 min, washed, and the retained [(3)H] extracted and assayed. Some tissues were treated with GABA uptake inhibitors (nipecotic acid or NO-711) prior to incubation. At concentrations of 0.1 and 1.0 microM the uptake of [(3)H]GABA was saturated after 90 min of incubation. At 10 microM, at least two uptake compartments were apparent, and the amount of [(3)H]GABA retained was five-fold greater than 0.1 microM. The uptake inhibitors reduced [(3)H]GABA accumulation by more than 80%. In the release study, pulp was incubated in [(3)H]GABA (0.5 microM) for 90 min, and superfused with Krebs solution containing NO-711 (5 microM). Electrical stimulation increased the overflow of [(3)H]; a GABA(B) autoreceptor agonist (baclofen) inhibited, whilst an antagonist, Sch 50911, enhanced this release. The effects of baclofen were reversed by Sch 50911. These results imply that GABA can be taken up and bound firmly in compartments within human dental pulp, GABA can be released from isolated pulp segments by electrical stimulation, and this release is modulated by GABA(B) autoreceptors.
Nassery
Khashayar
K
School of Dentistry, The University of Adelaide University, Adelaide, South Australia 5005, Australia.
Marino
Victor
V
Parker
David A S
DA
D000328:Adult; D017660:Autoreceptors / Q000187:drug effects / Q000378:metabolism; D001418:Baclofen / Q000494:pharmacology; D003782:Dental Pulp / Q000294:innervation / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D018682:GABA Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D006801:Humans; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009557:Nipecotic Acids / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D019275:Radiopharmaceuticals; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000187:drug effects / Q000493:pharmacokinetics*
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D017660:Autoreceptors; D018682:GABA Agents; D018755:GABA Agonists; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D009025:Morpholines; D009557:Nipecotic Acids; D010091:Oximes; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; D014316:Tritium; C078793:NNC 711; C030278:nipecotic acid; D005680:gamma-Aminobutyric Acid; D001418:Baclofen