Modulation of GABAA receptors and neuropeptide secretion by the neurosteroid allopregnanolone in posterior and intermediate pituitary.
A number of neurosteroids bind to GABAA receptors and alter their responsiveness to neurotransmitters. Considerable effort has been devoted to understanding how this form of receptor modulation alters inhibitory synaptic function. Neurosteroid-sensitive GABAA receptors have also been demonstrated in many endocrine cells, but little is known about how neurosteroids modulate the release of hormones. Here, the action of allopregnanolone, a neurosteroid that enhances GABAA receptor-mediated responses, was investigated in posterior pituitary nerve terminals and intermediate pituitary endocrine cells. Patch clamp recordings showed that GABA-evoked currents were enhanced to similar degrees and with similar concentration dependences in both locations. An organ bath preparation of the neurointermediate lobe was used to investigate drug effects on secretion of vasopressin and alpha-melanocyte stimulating hormone. GABA increased the basal release of vasopressin and alpha-melanocyte stimulating hormone from the posterior and intermediate pituitary lobe, respectively, an effect that could be blocked by picrotoxinin. Vasopressin release evoked by electrical stimulation was also examined, and a small statistically significant inhibition by 5 microM GABA was observed. Allopregnanolone increased the basal release of vasopressin, and this effect was blocked by the GABAA receptor antagonist picrotoxinin. Allopregnanolone had no effect in conjunction with GABA. In contrast to the posterior lobe, allopregnanolone had no effect on release from the intermediate lobe. Thus, allopregnanolone in physiological relevant concentrations modulates GABAA receptors in both the posterior and intermediate lobes, but only affects hormone release in the posterior lobe.
Hansen
Suzanne L
SL
Department of Pharmacology, The Danish University of Pharmaceutical Sciences, 2 Universitetsparken, 2100 Copenhagen, Denmark.
Fjalland
Bjarne
B
Jackson
Meyer B
MB
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism*; D010904:Pituitary Gland, Posterior / Q000187:drug effects* / Q000378:metabolism*; D011280:Pregnanolone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D013997:Time Factors; D014667:Vasopressins / Q000378:metabolism; D000521:alpha-MSH / Q000037:antagonists & inhibitors / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology
D018756:GABA Antagonists; D009479:Neuropeptides; D010852:Picrotoxin; D011280:Pregnanolone; D011963:Receptors, GABA-A; D014667:Vasopressins; D000521:alpha-MSH; D005680:gamma-Aminobutyric Acid