MECHANISMS FOR STIMULATION OF RAT ANTERIOR-PITUITARY-CELLS BY ARGININE AND OTHER AMINO-ACIDS

Arginine and other amino acids are secretagogues for growth hormone an d prolactin in the intact animal, but the mechanism of action is uncle ar. We have studied the effects of amino acids on cytosolic free calci um concentration ([Ca2+](i)) in single rat anterior pituitary (AP) cel ls. Arginine elicited a large increase of [Ca2+](i) in about 40 % of a ll the BP cells, suggesting that amino acids may modulate hormone secr etion by acting directly on the pituitary. 2. Cell typing by immunoflu orescence of the hormone the cells store showed that the arginine-sens itive cells are distributed uniformly within all the five;LP cell type s. The arginine sensitive cells overlapped closely with the subpopulat ion of cells sensitive to thyrotrophin-releasing hormone. 3. Other cat ionic as well as several neutral (dipolar) amino acids had the same ef fect as arginine. The increase of [Ca2+](i) was dependent on extracell ular Ca2+ and blocked by dihydropyridine, suggesting that it is due to Ca2+ influx through L-type voltage-gated Ca2+ channels. The [Ca2+](i) increase was also blocked by removal of extracellular Na+ but not by tetrodotoxin. The substrate specificity for stimulation of AP cells re sembled closely that of the amino acid transport system B-0,B-+. We pr opose that electrogenic amino acid influx through this pathway depolar izes the plasma membrane with the subsequent activation of voltage-gat ed Ca2+ channels and Ca2+ entry. 4. Amino acids also stimulated prolac tin secretion in vitro with a similar substrate specificity to that fo und for the [Ca2+](i) increase. Existing data on the stimulation of se cretion of other hormones by amino acids suggest that a similar mechan ism could apply to other endocrine glands.