Differentielle Regulation der postprandialen Jejunummotilität des Menschen durch CCK und durch das cholinerge Nervensystem

Summary of Study Protocol "Differential Regulation of Postprandial Human Jejunal Motility by CCK and the Cholinergic System". This study was designed to assess the role of endogenous CCK and cholinergic neural inputs as physiological regulators of human postprandial jejunal motility and transit. Therefore, CCK-A and muscarinic regulators were blocked by their specific antagonists loxiglumide and atropine. Methods: 9 healthy male volunteers were studied on 3 separate days in random order with background IV infusions of a) saline 0,9%, b) atropine [5µg / (kg x h)] or c) loxiglumide [10 mg / (kg x h)]. After an interdigestive period of at least 20 min a mixed liquid meal (49% carbohydrate, 35%liquid, 16%protein) was intrajejunally perfused for 240 min through the most proximal port of the manometry catheter (8 ports spaced at 2 cm-intervals) located just distally the ligament of Treitz. Intestinal transit time was measured by the hydrogen breath test with 15 g lactulose intrajejunally administered 1 min after start of nutrition perfusion. Results: Mean ± SEM ; * : p < 0,05 vs saline 0,9% ; # : p< 0,01 loxiglumid vs atropine. The results in following sequence of the parameter: Saline ; Atropin ; Loxiglumide. Summery of contraktions / 240 min: 5434 ±568 ; 5140 ± 768 ; 3414 ± 629*#. Mean amplitude (mmHg): 18,9 ± 0,9 ; 23,9 ± 1,1* ; 16,3 ± 1,0 *#. Mean duration(s): 3,7 ± 0,2 ; 3,4 ± 0,1* ; 3,2 ± 0,1*. Motility index (mmHg x s/240 min): 229248 ± 28446 ; 261446 ± 46120 ; 117587 ± 30879*#. summery of propagated peaks/240min: 3957 ± 448 ; 2798 ± 522* ; 1824 ± 479*. % propagated peaks / 240 min: 58,7 ± 2,4 ; 40,2 ± 3,2* ; 39,8± 4,4*. Summery of propagation over 2 cm: 920 ± 10 ; 785 ± 147 ; 505 ± 130*. Summery of propagation over 4 ?6 cm: 423 ± 50 ; 266 ± 56* ; 180 ± 59*. Summery of propagation over 8 ?12cm: 117 ± 24 ; 61 ± 10* ; 37 ± 10*. Intestinal transit time (min): 54,4 ± 11,3 ; 123,3 ± 24,8* ; 164,4 ± 24,1*. Summary of results: Atropine did not alter overall contraction frequency and motility index. It increased amplitude but shortened duration of contractions. It markedly reduced the proportion of propagated contractions and especially propagation over longer distandes in the jejunum. Loxiglumide clearly diminished frequency, amplitude and duration of contractions, absolute number and percentage of propagated contractions. Both atropine and loxiglumide, markedly delayed small intestinal transit. Conclusions: Both, endogenous CCK and cholinergic neural input are important determinants of intestianl transit. However, they differently affect human postprandial jejunal motility. CCK is an important stimulatory regulator of motility activity (frequency, amplitude and duration) and its spatial temporal organization (wave propagation). Cholinergic input is not a major stimulatory regulator of motility activity but is required for prograde wave propagation, especially over longer distances. Intestinal transit depends clearly more on organization than on activity of the contractile pattern. The differential effects of loxiglumide and atropine would be compatible with the notion that endogenous CCK does not primarily affect jejunal motility via receptors on cholinergic neurons but mainly interacts with CCK-A receptors directly located on smooth muscle.