Biphasic effect of GABAA receptor agonists on prolactin secretion: evidence for two types of GABAA receptor complex on lactotrophes

The effects of GABA receptor agonists on prolactin secretion in vitro was examined using a rapid superfusion system. GABA and muscimol caused a biphasic effect on prolactin secretion, both components of which were antagonised by bicuculline methiodide, while baclofen had no effect on basal or stimulated secretion, demonstrating the GABAA receptor specificity of both components. Homocarnosine caused only inhibition of secretion, and a range of partly rigid GABA analogues were relatively poor at causing stimulation of secretion. Both effects of muscimol were antagonised by low-chloride medium and the anion channel blocker DIDS, but strychnine and picrotoxinin were both potent and selective antagonists of the stimulatory effect. These results demonstrate a novel biphasic effect of GABAA agonists or prolactin secretion, the two components of which appear to be independent and mediated by different types or states of GABAA receptor/chloride channel complex.