Mechanism of D(2) agonist-induced inhibition of GH secretion from human GH-secreting adenoma cells.
The mechanism of dopamine D(2) agonist-induced inhibition of GH secretion from GH-secreting adenoma cells was investigated by measurement of intracellular calcium concentration ([Ca(2+)] (i)) and static incubation experiment. Bromocriptine decreased [Ca(2+)](i) in a concentration-dependent manner through D(2) receptor. The inhibition was abolished by pertussis toxin pretreatment. Bromocriptine did not decrease [Ca (2+)](i) after nitrendipine had decreased it. 8Br-cAMP increased [Ca(2+)](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 D(2) 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.
Nishina
Yuko
Y
Department of Nephrology and Endocrinology, University of Tokyo Faculty of Medicine, Tokyo.
Takano
Koji
K
Yasufuku-Takano
Junko
J
Teramoto
Akira
A
Fujita
Toshiro
T
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000236:Adenoma / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D001971:Bromocriptine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D009568:Nitrendipine / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D015222:Sodium Channels; D019382:Human Growth Hormone; D015124:8-Bromo Cyclic Adenosine Monophosphate; D001971:Bromocriptine; D009568:Nitrendipine; D037342:Pertussis Toxin; D002118:Calcium