Effects of substance P on human colonic mucosa in vitro

被引:78
作者
Riegler, M
Castagliuolo, I
So, PTC
Lotz, M
Wang, C
Wlk, M
Sogukoglu, T
Cosentini, E
Bischof, G
Hamilton, G
Teleky, B
Wenzl, E
Matthews, JB
Pothoulakis, C
机构
[1] Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA
[2] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA
[3] MIT, Dept Mech Engn, Cambridge, MA 02139 USA
[4] Univ Vienna, Vienna Gen Hosp, Surg Clin, A-1090 Vienna, Austria
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 1999年 / 276卷 / 06期
关键词
genistein; histamine; short-circuit current; neurokinin; 1; receptor;
D O I
10.1152/ajpgi.1999.276.6.G1473
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Previous studies indicated that the peptide substance P (SP) causes Cl--dependent secretion in animal colonic mucosa. We investigated the effects of SP in human colonic mucosa mounted in Ussing chamber. Drugs for pharmacological characterization of SP-induced responses were applied 30 min before SP. Serosal, but not luminal, administration of SP (10(-8) to 10(-6) M) induced a rapid, monophasic concentration and Cl--dependent, bumetanide-sensitive short-circuit current (I-sc) increase, which was inhibited by the SP neurokinin 1 (NK1)-receptor antagonist CP-96345, the neuronal blocker TTX, the mast cell stabilizer lodoxamide, the histamine 1-receptor antagonist pyrilamine, and the PG synthesis inhibitor indomethacin. SP caused TTX- and lodoxamide-sensitive histamine release from colonic mucosa. Two-photon microscopy revealed NK1 (SP)-receptor immunoreactivity on nerve cells. The tyrosine kinase inhibitor genistein concentration dependently blocked SP-induced I-sc increase without impairing forskolin- and carbachol-mediated I-sc increase. We conclude that SP stimulates Cl--dependent secretion in human colon by a pathway(s) involving mucosal nerves, mast cells, and the mast cell product histamine. Our results also indicate that tyrosine kinases may be involved in this SP-induced response.
引用
收藏
页码:G1473 / G1483
页数:11
相关论文
共 61 条
[1]
IMMUNE-SYSTEM CONTROL OF RAT AND RABBIT COLONIC ELECTROLYTE TRANSPORT - ROLE OF PROSTAGLANDINS AND ENTERIC NERVOUS-SYSTEM [J].
BERN, MJ ;
STURBAUM, CW ;
KARAYALCIN, SS ;
BERSCHNEIDER, HM ;
WACHSMAN, JT ;
POWELL, DW .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (06) :1810-1820
[2]
FIBROBLASTS MODULATE INTESTINAL SECRETORY RESPONSES TO INFLAMMATORY MEDIATORS [J].
BERSCHNEIDER, HM ;
POWELL, DW .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 89 (02) :484-489
[3]
EFFECTS OF TETRODOTOXIN ON CHLORIDE SECRETION IN RABBIT DISTAL COLON - TISSUE AND CELLULAR STUDIES [J].
BIAGI, B ;
WANG, YZ ;
COOKE, HJ .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 258 (02) :G223-G230
[4]
MECHANISM OF ELECTRONEUTRAL SODIUM-CHLORIDE ABSORPTION IN DISTAL COLON OF THE RAT [J].
BINDER, HJ ;
FOSTER, ES ;
BUDINGER, ME ;
HAYSLETT, JP .
GASTROENTEROLOGY, 1987, 93 (03) :449-455
[5]
BISSONETTE EY, 1993, IMMUNOPHARMACOLOGY G, P95
[6]
DIRECT OBSERVATION OF SUBSTANCE-P-INDUCED INTERNALIZATION OF NEUROKININ-1 (NK1) RECEPTORS AT SITES OF INFLAMMATION [J].
BOWDEN, JJ ;
GARLAND, AM ;
BALUK, P ;
LEFEVRE, P ;
GRADY, EF ;
VIGNA, SR ;
BUNNETT, NW ;
MCDONALD, DM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (19) :8964-8968
[7]
BROWN DR, 1992, J PHARMACOL EXP THER, V261, P1206
[8]
Neurokinin-1 (NK-1) receptor is required in Clostridium difficile-induced enteritis [J].
Castagliuolo, I ;
Riegler, M ;
Pasha, A ;
Nikulasson, S ;
Lu, B ;
Gerard, C ;
Gerard, NP ;
Pothoulakis, C .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (08) :1547-1550
[9]
NEURONAL INVOLVEMENT IN THE INTESTINAL EFFECTS OF CLOSTRIDIUM-DIFFICILE TOXIN-A AND VIBRIO-CHOLERAE ENTEROTOXIN IN RAT ILEUM [J].
CASTAGLIUOLO, I ;
LAMONT, JT ;
LETOURNEAU, R ;
KELLY, C ;
OKEANE, JC ;
JAFFER, A ;
THEOHARIDES, TC ;
POTHOULAKIS, C .
GASTROENTEROLOGY, 1994, 107 (03) :657-665
[10]
Increased substance P responses in dorsal root ganglia and intestinal macrophages during Clostridium difficile toxin A enteritis in rats [J].
Castagliuolo, I ;
Keates, AC ;
Qiu, BS ;
Kelly, CP ;
Nikulasson, S ;
Leeman, SE ;
Pothoulakis, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (09) :4788-4793