Mechanisms for stimulation of rat anterior pituitary cells by arginine and other amino acids.

1. Arginine and other amino acids are secretagogues for growth hormone and prolactin in the intact animal, but the mechanism of action is unclear. We have studied the effects of amino acids on cytosolic free calcium concentration ([Ca2+]i) in single rat anterior pituitary (AP) cells. Arginine elicited a large increase of [Ca2+]i) in about 40% of all the AP cells, suggesting that amino acids may modulate hormone secretion by acting directly on the pituitary. 2. Cell typing by immunofluorescence of the hormone the cells store showed that the arginine-sensitive cells are distributed uniformly within all the five AP cell types. The arginine-sensitive cells overlapped closely with the subpopulation of cells sensitive to thyrotrophin-releasing hormone. 3. Other cationic as well as several neutral (dipolar) amino acids had the same effect as arginine. The increase of [Ca2+]i was dependent on extracellular 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 resembled closely that of the amino acid transport system B0+. We propose that electrogenic amino acid influx through this pathway depolarizes the plasma membrane with the subsequent activation of voltage-gated Ca2+ channels and Ca2+ entry. 4. Amino acids also stimulated prolactin secretion in vitro with a similar substrate specificity to that found for the [Ca2+]i increase. Existing data on the stimulation of secretion of other hormones by amino acids suggest that a similar mechanism could apply to other endocrine glands.