CHARACTERIZATION OF THE ANTIGEN-INDUCED CONTRACTION OF COLONIC SMOOTH-MUSCLE FROM SENSITIZED GUINEA-PIGS

被引:15
作者
BARNETTE, MS
GROUS, M
机构
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1992年 / 262卷 / 01期
关键词
COLON; OVALBUMIN; HISTAMINE; SEROTONIN; LEUKOTRIENES;
D O I
10.1152/ajpgi.1992.262.1.G144
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
To study the potential of inflammatory mediators to alter colonic motility, we characterized the response of distal colonic smooth muscle to antigen challenge. Addition of ovalbumin to isolated segments of circular smooth muscle obtained from sensitized guinea pigs produced a biphasic contraction. The initial response consisted of a rapid contraction followed by a late response, which was a more sustained but smaller increase in tone and phasic activity. Interestingly, these two responses could be antagonized differentially. Pretreatment with mepyramine (10-mu-M) inhibited the initial response, whereas the leukotriene antagonist WY 48252 (10-mu-M) inhibited the late response. The mast cell stabilizer doxantrazole (0.1-mu-M) reduced only the late response. Inhibition of cyclooxygenase with meclofenamic acid (1-mu-M) potentiated both responses, whereas blocking neuronal activity with tetrodotoxin (1-mu-M) only enhanced the initial response. These data indicate clear differences between the inflammatory mediators important in the initial vs. the late response. The initial response is probably mediated by the release of histamine, with enteric neuronal interactions important in attenuating the magnitude of this response. In contrast, the late response appears to be mediated by the release of peptidyl leukotrienes. In this system, cyclooxygenase products apparently function to decrease the response of the smooth muscle to these mediators. These results suggest that release of mediators during an inflammatory response could profoundly alter colonic motility and that these alterations may be important in the pathophysiological manifestations associated with colonic inflammation. Furthermore, our results demonstrate that various regions of the gut respond differently to antigen challenge and that it may not be possible to extrapolate the findings obtained from a single region of the gut to explain inflammatory changes occurring throughout the gastrointestinal system.
引用
收藏
页码:G144 / G149
页数:6
相关论文
共 24 条
[1]  
ADAMS GK, 1985, AM REV RESPIR DIS, V131, P8
[2]   MEDIATORS OF ANAPHYLAXIS-INDUCED ION-TRANSPORT CHANGES IN SMALL-INTESTINE [J].
CASTRO, GA ;
HARARI, Y ;
RUSSELL, D .
AMERICAN JOURNAL OF PHYSIOLOGY, 1987, 253 (04) :G540-G548
[3]  
COLLINS S M, 1989, Gastroenterology, V96, pA95
[4]  
COLLINS SM, 1989, INFLAMM BOWEL DIS, P59
[5]   SITES OF ACTION OF 5-HYDROXYTRYPTAMINE IN NERVE-MUSCLE PREPARATIONS FROM THE GUINEA-PIG SMALL-INTESTINE AND COLON [J].
COSTA, M ;
FURNESS, JB .
BRITISH JOURNAL OF PHARMACOLOGY, 1979, 65 (02) :237-248
[6]  
DELBALZO U, 1989, J PHARMACOL EXP THER, V248, P1003
[7]   5-HT - THE ENIGMA VARIATIONS [J].
FOZARD, JR .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1987, 8 (12) :501-506
[8]   2 KINDS OF TRYPTAMINE RECEPTOR [J].
GADDUM, JH ;
PICARELLI, ZP .
BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY, 1957, 12 (03) :323-328
[9]  
GARATTINI S, 1965, SEROTONIN, P105
[10]   THE EFFECT OF LEUKOTRIENE-D4 ON THE ISOLATED STOMACH AND COLON OF THE RAT [J].
GOLDENBERG, MM ;
SUBERS, EM .
LIFE SCIENCES, 1983, 33 (21) :2121-2127