Mechanism of D2 agonist-induced inhibition of GH secretion from human GH-secreting adenoma cells

Abstract

The mechanism of dopamine D2 agonist-induced inhibition of GH secretion from GH-secreting adenoma cells was investigated by measurement of intracellular calcium concentration ([Ca2+]i) and static incubation experiment. Bromocriptine decreased [Ca2+]i in a concentration-dependent manner through D2 receptor. The inhibition was abolished by pertussis toxin pretreatment. Bromocriptine did not decrease [Ca2+]i after nitrendipine had decreased it. 8Br-cAMP increased [Ca2+]i but application of bromocriptine decreased it, suggesting that bromocriptine-induced inhibition of [Ca 2+]i is not dependent on bromocriptine-induced inhibition of adenylyl cyclase. Static incubation experiment revealed that bromocriptine inhibited GH secretion in a concentration-dependent manner. The inhibition was through D2 receptor and was abolished by pertussis toxin pretreatment. 8Br-cAMP increased GH secretion. Bromocriptine decreased GH secretion even after 8Br-cAMP pretreatment. However, the GH release from cells incubated with bromocriptine alone was significantly less than that from cells incubated with bromocriptine after 8Br-cAMP pretreatment, suggesting a modulatory action of cAMP system in bromocriptine response.