Electrophysiological characterization of GABAA receptors in anterior pituitary cells of newborn rats.
The gamma-aminobutyric acid (GABA)-ergic communication between the CNS and the anterior pituitary gland has been documented in numerous histochemical and biochemical studies but electrophysiological studies characterizing the GABAA receptor in the anterior pituitary are still lacking. In the present report we studied the GABA-induced current responses in cultured cells from the anterior pituitary gland of 6- to 10-day-old rats using the patch-clamp technique in the whole cell configuration. Fast application of GABA (100 microM) induced membrane currents in 90% of cells in 2-day-old cultures. The EC50 for GABA was 22.9 microM and the Hill coefficient was 1.8. The responses to GABA (10 microM) were inhibited by bicuculline (2 microM) to 14%, by picrotoxin (5 microM) to 21% and by zinc (10 microM) to 33%. Inhibition to 56% was observed with 6 microM strychnine. The GABA responses were sensitive to diazepam and pentobarbital. Half-maximal potentiation of responses to GABA (10 microM) was found with 1.0 microM diazepam and with 14.4 microM pentobarbital. The maximal potentiation of GABA responses was 222% for diazepam and 195% for pentobarbital. Pentobarbital (100 microM) did not induce any response in anterior pituitary cells in the absence of GABA. The application of GABA at concentrations 10 microM or higher, induced membrane currents that desensitized. Desensitization proceeded as a biexponential process with estimated fast and slow time constants which decreased with concentration. The responses to GABA (300 microM) desensitized to 93% with time constants of 1.4 and 5.3 s. Half-maximal desensitization was found with 13.4 microM GABA.(ABSTRACT TRUNCATED AT 250 WORDS)
Zemková
H
H
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague.
Vanĕcek
J
J
Krůsek
J
J
D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D003975:Diazepam / Q000494:pharmacology; D004361:Drug Tolerance; D004553:Electric Conductivity; D004594:Electrophysiology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000502:physiology*; D051381:Rats; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001640:Bicuculline; D003975:Diazepam; D018756:GABA Antagonists; D010424:Pentobarbital; D010852:Picrotoxin; D018079:Receptors, GABA; D015032:Zinc; D005680:gamma-Aminobutyric Acid