Schubert M L, Hightower J
Department of Medicine, Medical College of Virginia, Richmond.
Am J Physiol. 1990 Jun;258(6 Pt 1):G982-7. doi: 10.1152/ajpgi.1990.258.6.G982.
The present study was designed to examine the mode of action of muscarinic agonists on somatostatin secretion in intact gastric tissues, i.e., mucosal segments from the fundus and antrum of rat and the isolated luminally perfused mouse stomach. Methacholine caused similar decreases in somatostatin secretion in segments from the fundus (35 +/- 3%; P less than 0.001) and antrum (35 +/- 2%; P less than 0.001) of rat stomach, and in whole mouse stomach (43 +/- 3%; P less than 0.001). The decrease was the net effect of a dominant inhibition and a lesser stimulation of somatostatin secretion. Pretreatment with the permeant derivative of the acetomethoxy ester form of the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA/AM, 15 microM) caused a further decrease in methacholine-induced somatostatin secretion, implying that a stimulatory component existed that was mediated by intracellular calcium. Pretreatment with pertussis toxin (125 ng/ml) for 60 min converted the decrease in somatostatin secretion to an increase above basal levels. The increase induced by pretreatment with pertussis toxin was abolished by additional pretreatment with BAPTA/AM. Procaine (5 mM), which blocks release of calcium from intracellular stores, produced an effect on somatostatin secretion similar to that of BAPTA/AM. The results indicate that 1) methacholine exerts dual inhibitory and stimulatory effects on somatostatin cells of rat and mouse stomach, 2) the dominant effect is inhibitory and sensitive to pertussis toxin, and 3) a concurrent stimulatory effect, mediated by calcium, is unmasked after blockade of the inhibitory effect with pertussis toxin.
本研究旨在探讨毒蕈碱激动剂对完整胃组织中生长抑素分泌的作用模式，即大鼠胃底和胃窦的黏膜段以及分离的经腔内灌注的小鼠胃。乙酰甲胆碱使大鼠胃底段（35±3%；P<0.001）、胃窦段（35±2%；P<0.001）以及整个小鼠胃（43±3%；P<0.001）中的生长抑素分泌出现类似程度的下降。这种下降是生长抑素分泌受主要抑制和较小刺激的综合作用结果。用钙螯合剂1,2-双（2-氨基苯氧基）乙烷-N,N,N',N'-四乙酸（BAPTA/AM，15微摩尔）的乙酰甲氧基酯形式的渗透性衍生物进行预处理，导致乙酰甲胆碱诱导的生长抑素分泌进一步下降，这意味着存在一种由细胞内钙介导的刺激成分。用百日咳毒素（125纳克/毫升）预处理60分钟后，生长抑素分泌的下降转变为高于基础水平的增加。用BAPTA/AM进行额外预处理可消除百日咳毒素预处理所诱导的增加。普鲁卡因（5毫摩尔）可阻断细胞内钙库释放钙，其对生长抑素分泌的影响与BAPTA/AM类似。结果表明：1）乙酰甲胆碱对大鼠和小鼠胃的生长抑素细胞发挥双重抑制和刺激作用；2）主要作用是抑制性的且对百日咳毒素敏感；3）在用百日咳毒素阻断抑制作用后，由钙介导的同时存在的刺激作用得以显现。
