In vivo and in vitro effects of tetrahydroisoquinolines and other alkaloids on rat pituitary function.

Several tetrahydroisoquinolines (TIQs) were tested for their in vitro and in vivo capacities to modulate prolactin (PRl) and beta-endorphin (beta-end) secretion by the rat pituitary and for their abilities to displace [3H]spiroperidol and [3H]naloxone binding from pituitary and hypothalamic membranes. Receptor binding studies showed that TIQs could be classified as having (a) higher affinity for opiate receptors (tetrahydropapaverine, papaverine, 6-methylsalolinol, 1-carboxysalsolinol and 3',4'-deoxy-norlaudanosolinecarboxylic acid), (b) higher affinity for the dopamine receptor (salsolinol and 7-methylsalsolinol), or (c) approximately equal affinity for the two binding sites (6,7-dimethylsalsolinol and tetrahydropapaveroline, THP). In freely moving male rats, THP produced a several-fold increase in plasma PRL levels. This effect was not altered by co-administration of naloxone but was attenuated by dopamine. In vitro several TIQs reversed the inhibitory effect of dopamine on PRL secretion by cultured anterior pituitary cells. The order of potencies of the TIQs in this system paralleled their order of potencies in the dopamine receptor assay. THP, the most potent dopamine antagonist, also blocked dopamine-mediated inhibition of beta-endorphin secretion from neurointermediate lobe cells in culture. These data demonstrate that THP and some other TIQs can act as dopamine antagonists in radioreceptor assays, in cell culture and in vivo.