Endogenous CCK depresses contractile activity within the ascending myenteric reflex pathway of rat ileum. 2003

M Storr, and D Sattler, and A Hahn, and V Schusdziarra, and H D Allescher
Department of Internal Medicine II, Technical University of Munich, Ismaningerstrasse 22, 81675 Munich, Germany. martin.storr@ltz.tum.de

The ascending excitatory reflex is an important part of the myenteric reflex. In order to study the ascending neural pathways, isolated segments of rat ileum were stimulated by electrical stimulation of the gut wall (20 V, 3 pulses per second, 1 ms) using platinum electrodes. The excitatory contractile response was recorded using perfused manometric side-hole tubing located 2 and 4 cm orally to the stimulation site. The contractile response to electrical stimulation was abolished by atropine (10(-6) M) or hexamethonium (10(-4) M). The excitatory response increased after administration of the cholecystokinin A (CCK(A)) receptor antagonists lorglumide (3x10(-6) M: +44.1%), devazepide (10(-8) M: +19.4%; 10(-7) M: +30.0%) and SR-27897 (10(-10) M: +21.8%, 10(-8) M: +47.0%, P<0.05, n=8). However, the CCK(B) receptor antagonist L-365,260 also caused a significant increase in the oral excitation (10(-6) M: +27.4%). sCCK-8 caused a significant reduction in the ascending response (10(-8) M: -11.5%) and induced spontaneously occurring contractions at doses ranging from 10(-10)-10(-6) M. CCK-9 significantly increased the ascending response (10(-7) M: +10.9%, P<0.05). However, caerulein (10(-10) M: -25.9%, 10(-8) M: -26.8%; P<0.01) and pentagastrin (10(-10) M: -20.2%, P<0.05; 10(-8) M: -23.7%, P<0.01; 10(-6) M: -28.3%, P<0.001) reduced the ascending contractile response significantly. These data, obtained with potent and highly specific CCK receptor antagonists, demonstrate an inhibitory role of endogenously released CCK within the ascending neural pathway. The data further suggest that exogenously applied CCK-related peptides have different effects on the myenteric reflex which might be due to excitation of the different involved neurons (short and long ascending inter- and motorneurons) in an unphysiological order. Thus in experiments investigating more complex neuronal circuits, experiments with antagonists should be regarded as more specific.

UI MeSH Term Description Entries
D007082 Ileum The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.
D008297 Male Males
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009197 Myenteric Plexus One of two ganglionated neural networks which together form the ENTERIC NERVOUS SYSTEM. The myenteric (Auerbach's) plexus is located between the longitudinal and circular muscle layers of the gut. Its neurons project to the circular muscle, to other myenteric ganglia, to submucosal ganglia, or directly to the epithelium, and play an important role in regulating and patterning gut motility. (From FASEB J 1989;3:127-38) Auerbach's Plexus,Auerbach Plexus,Auerbachs Plexus,Plexus, Auerbach's,Plexus, Myenteric
D009434 Neural Pathways Neural tracts connecting one part of the nervous system with another. Neural Interconnections,Interconnection, Neural,Interconnections, Neural,Neural Interconnection,Neural Pathway,Pathway, Neural,Pathways, Neural
D010418 Pentagastrin A synthetic pentapeptide that has effects like gastrin when given parenterally. It stimulates the secretion of gastric acid, pepsin, and intrinsic factor, and has been used as a diagnostic aid. Acignost,Gastrin Pentapeptide,Peptavlon,Pentapeptide, Gastrin
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010528 Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Peristalses
D011949 Receptors, Cholecystokinin Cell surface proteins that bind cholecystokinin (CCK) with high affinity and trigger intracellular changes influencing the behavior of cells. Cholecystokinin receptors are activated by GASTRIN as well as by CCK-4; CCK-8; and CCK-33. Activation of these receptors evokes secretion of AMYLASE by pancreatic acinar cells, acid and PEPSIN by stomach mucosal cells, and contraction of the PYLORUS and GALLBLADDER. The role of the widespread CCK receptors in the central nervous system is not well understood. CCK Receptors,Caerulein Receptors,Cholecystokinin Octapeptide Receptors,Cholecystokinin Receptors,Pancreozymin Receptors,Receptors, CCK,Receptors, Caerulein,Receptors, Pancreozymin,Receptors, Sincalide,Sincalide Receptors,CCK Receptor,CCK-4 Receptors,CCK-8 Receptors,Cholecystokinin Receptor,Receptors, CCK-4,Receptors, CCK-8,Receptors, Cholecystokinin Octapeptide,CCK 4 Receptors,CCK 8 Receptors,Octapeptide Receptors, Cholecystokinin,Receptor, CCK,Receptor, Cholecystokinin,Receptors, CCK 4,Receptors, CCK 8

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