The electrical properties of isolated human prolactin-secreting adenoma cells and their modification by dopamine.
Human prolactinoma cells were maintained in culture for a period of at least 8 days and were able to secrete PRL in large amounts. This secretion was inhibited by bromocriptine, an agonist of dopaminergic receptors, in a dose-dependent manner. The cells showed electrical activity (action potentials) which was blocked by inhibitors of calcium current (cobalt, manganese), whereas it was insensitive to blockers of sodium current (tetrodotoxin). At the resting potential of the cell, dopamine induced a hyperpolarizing response such that action potentials no longer occurred. This effect was due to increase of the membrane conductance and depended on the cell potential. The reversal potential of this response was at -100 mV, which suggests the involvement of potassium ions. Bromocriptine and RU 24213, which are strong dopaminergic receptor agonists, both induced responses identical to the dopamine-induced response. The D2 receptor antagonists (haloperidol, domperidone, and spiperone) blocked the dopamine-induced response in a reversible manner. The D1 antagonist of dopaminergic receptors flupentixol had no effect on the dopamine response. It is concluded that the dopamine modulation of electrical activity involving calcium current may be an early important step in the mechanism by which dopamine inhibits PRL release.
D000236:Adenoma / Q000378:metabolism / Q000503:physiopathology*; D001971:Bromocriptine / Q000494:pharmacology; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005475:Flupenthixol / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials; D010627:Phenethylamines / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D011388:Prolactin / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism; D013134:Spiperone / Q000494:pharmacology; D013997:Time Factors
D010627:Phenethylamines; D011954:Receptors, Dopamine; D001971:Bromocriptine; D013134:Spiperone; D004294:Domperidone; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride; D011388:Prolactin; D005475:Flupenthixol; D006220:Haloperidol; D004298:Dopamine