Bibliothek

Notizen: Abstract: The present study demonstrates that 3,4-dihydroxyphenylethylamine (DA, dopamine) prevents neurotensin (NT) stimulation of both prolactin (PRL) release and calcium influx by interacting with specific receptors that are functionally linked to calcium channels. As shown by the studies with dispersed cells from rat anterior pituitary, the pharmacology of the control of PRL release and calcium influx, both induced by NT, was found to be typical of a DAergic process. This was demonstrated (1) by the order of potency of agonists in inhibiting PRL release and calcium influx (DA 〉 epinephrine 〉 norepinephrine isoproterenol); (2) by the high affinity of antagonists such as haloperidol and fluphenazine for this process; and (3) by the high degree of stereoselectivity of sulphide. Specific D2 receptor agonists, such as bromocriptine and lisuride, and the specific D2 receptor antagonist (-)-sulpiride were found to be highly potent on the DA receptors negatively coupled with calcium channels and PRL release. DA was found to lack the capacity to change the influx of calcium induced by either the sodium channel activator veratridine or high extracellular potassium levels, thus indicating a specific action of this amine on calcium channels sensitive to NT. In a range of concentrations that are effective in inhibiting either the calcium influx or the PRL release, both induced by NT, DA did not alter the cyclic AMP generating system. DA (from 1.0 nM to 50 nM) did not affect adenylate cyclase activity in rat pituitary gland homogenates and did not modify intracellular cyclic AMP levels in pituitary cells. The putative correlation between DA suppressing activity of the NT effects and the adenylate cyclase system was verified in pertussis toxin-treated pituitary cells. At the time that DA receptors negatively coupled to inhibition of adenylate cyclase were not operative, DA was still fully effective in preventing NT stimulation of PRL release. The lack of effect of low concentrations of DA on both basal adenylate cyclase activity and cyclic AMP content in pituitary cells, together with their capacity to inhibit the NT effects in pertussis toxin-treated cells, suggest that DA may act independently of cyclic AMP in the control of PRL secretion. These observations lead to the hypothesis of the existence of two inhibitory mechanisms for DA in mammotrophs.