Chang E B, Brown D R, Wang N S, Field M
J Clin Invest. 1986 Jul;78(1):281-7. doi: 10.1172/JCI112562.
Substance P (SP), neurotensin (NT), bombesin (BB), serotonin (5HT), and carbamylcholine (CCH) transiently increase electrogenic anion secretion in chinchilla and chicken ileum. SP and CCH also transiently inhibit amiloride-sensitive Na/H exchange in isolated chicken enterocytes. Loperamide (LP) inhibits the short-circuit current responses caused by SP, NT, and BB, but not those caused by CCH, 5HT, Ca ionophore, or cyclic nucleotides. Similarly, LP inhibits the effects of SP, but not those of CCH, on Na/H exchange. LP inhibition of the SP effects was further studied in isolated chicken enterocytes. CCH and SP transiently increased cytosolic Ca activity by 20-50 nmol/liter, but only the response to SP was inhibited by LP (10(-5) M) and by the absence of extracellular Ca. We conclude SP and CCH effects on intestinal electrolyte transport are mediated by increasing enterocyte Ca activity and LP specifically inhibits peptide hormone-activated Ca entry by an opiate receptor-independent mechanism.
P物质(SP)、神经降压素(NT)、蛙皮素(BB)、5-羟色胺(5HT)和氨甲酰胆碱(CCH)可使灰鼠和鸡回肠的电生性阴离子分泌短暂增加。SP和CCH还可短暂抑制分离的鸡肠上皮细胞中对氨氯吡脒敏感的Na⁺/H⁺交换。洛哌丁胺(LP)可抑制由SP、NT和BB引起的短路电流反应,但不抑制由CCH、5HT、钙离子载体或环核苷酸引起的反应。同样,LP可抑制SP对Na⁺/H⁺交换的作用,但不抑制CCH的作用。在分离的鸡肠上皮细胞中进一步研究了LP对SP作用的抑制情况。CCH和SP可使细胞溶质Ca²⁺活性短暂增加20 - 50 nmol/升,但只有对SP的反应可被LP(10⁻⁵ M)和细胞外Ca²⁺缺失所抑制。我们得出结论,SP和CCH对肠道电解质转运的作用是通过增加肠上皮细胞Ca²⁺活性介导的,且LP通过一种不依赖阿片受体的机制特异性抑制肽类激素激活的Ca²⁺内流。