The effects of domperidone on prolactin secretion from the anterior pituitary glands of female rats were studied. A perifusion system and radioimmunoassay were used to study secretion; static incubations and incorporation of [3H]leucine were used to measure biosynthesis. During perifusion, intact anterior lobes showed a constant rate of prolactin secretion for up to 5 h (after a 90-min preincubation to stabilize the tissue). Incorporation studies revealed an increase in protein synthesis in perifused hemipituitary glands. When glands were treated with 10 nm-domperidone, prolactin secretion began to decline after the first hour, reaching a maximum of 40–50% inhibition after a further 90 min. Growth hormone secretion showed no such decline. Inhibition of prolactin secretion continued for up to 2 h after withdrawal of the drug. Treatment with 100 nm-dopamine resulted in a more rapid inhibition of secretion, but the effect was reversed on withdrawal of the catecholamine. The prolactin content of perifused hemipituitary glands was measured after treatment with domperidone; the contents of control and treated glands did not differ, but were depleted compared with hemipituitary glands which had not been perifused.
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