Responses of human sling and clasp fibers to cholecystokinin (CCK) and gastrin through CCK receptors.
OBJECTIVE
Cholecystokinin (CCK) and gastrin exert their influences via CCK receptors. This research was conducted to look at the responses of the sling and clasp fibers forming the human lower esophageal sphincter (LES) to CCK and gastrin, and the role of CCK receptors in the responses.


METHODS
Muscle strips of sling and clasp fibers from the LES were obtained from patients undergoing subtotal esophagectomy. Isometric tension responses of the strips to CCK-8 and gastrin-17 were studied, and the maximum effect (E(max)) for each agonist was derived. CCK-A receptor antagonist, CR1409 and CCK-B antagonist, CR2945 were applied to sling and clasp fibers and their pK(B) values were calculated.


RESULTS
Sling fibers produced significant contractions following exposure to CCK-8 and gastrin-17, while clasp fibers had less responses to the two agents. CR1409 and CR2945 inhibited responses of sling to CCK-8 in a concentration-dependent fashion. The inhibition effects of the two antagonists on clasp fibers were not measurable because there was a mild contraction of the fiber in response to CCK-8.


CONCLUSIONS
The contractions generated by sling fibers following exposure to CCK and gastrin are greater than that produced by clasp fibers. CCK-A receptors are more important for the generation of contractions by the sling fibers, whereas both CCK-A and CCK-B receptors are involved in the functional regulation of the clasp fibers. [Corrections added after online publication 28 April 2008: in the Background and Aims section of the preceding abstract, all instances of 'CKK' were corrected to 'CCK'. In the final sentence of the abstract 'CCKA'was corrected to 'CCK-A'. In the article title '(CKK)' was corrected to '(CCK)'.].
Liu
Jun-Feng
JF
Department of Thoracic Surgery, Fourth Hospital, Hebei Medical University, Shijiazhuang, China. liujf@heinfo.net
Gao
Li-Ping
LP
Wen
Shi-Wang
SW
Lu
Hui-Lai
HL
Zhang
Jian
J
Sun
Jian
J
Zhang
Shao-Wei
SW
Wang
Qi-Zhang
QZ
D000328:Adult; D001569:Benzodiazepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D049630:Esophageal Sphincter, Lower / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D005755:Gastrins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012844:Sincalide / Q000378:metabolism*
C116183:CR 2945; D005755:Gastrins; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D001569:Benzodiazepines; C013550:gastrin 17; D011377:Proglumide; C048181:lorglumide; D012844:Sincalide