Effect of the GABAA agonist muscimol on prolactin secretion from human prolactin-secreting adenomas and GH3 rat pituitary tumour cells.
The effect of muscimol, a specific potent GABAA receptor agonist, on prolactin release from human prolactin-secreting tissue was investigated using a perifusion system. Perifusion studies on normal rat anterior pituitary tissue, which has identical GABA receptors to those found in normal human pituitary glands, show that muscimol has a specific biphasic effect on prolactin release. This is characterized by an initial transient stimulation (222.3 +/- 21.6% of basal) lasting for 5-10 min followed by a more prolonged inhibitory phase (63.9 +/- 3.1% inhibition of basal). Five human prolactin-secreting adenomas were studied, and in none of the tumours could a biphasic response be demonstrated. One of the prolactin-secreting adenomas had a blunted inhibitory response, but the other 4 showed no inhibitory effect of muscimol on prolactin release. Muscimol had no significant effect on basal or thyrotropin-releasing-hormone (TRH)-stimulated prolactin secretion from GH3 rat pituitary tumour cells. These studies suggest that the GABAergic effect on prolactin secretion is absent or altered in both rat and human prolactin-secreting tumour cells.
Jones
T H
TH
Department of Medicine, University of Sheffield, UK.
Brown
B L
BL
Cullen
D R
DR
Dobson
P R
PR
D000328:Adult; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009118:Muscimol / Q000494:pharmacology*; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D015175:Prolactinoma / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology; D013973:Thyrotropin-Releasing Hormone
D011963:Receptors, GABA-A; D009118:Muscimol; C017069:bicuculline methiodide; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D001640:Bicuculline