title: Cholinergic transmission to colonic circular muscle of children with slow-transit constipation is unimpaired, but transmission via NK2 receptors is lacking.
abstract: Tachykinins (TKs) colocalize with acetylcholine in excitatory motor neurones supplying human colonic circular muscle (CCM). Some children with slow-transit constipation (STC) have reduced TK-immunoreactivity in nerve terminals in CCM suggesting a deficit in neuromuscular transmission. This study aimed to test this possibility. Seromuscular biopsies of transverse colon were obtained laparoscopically from STC children (37, 17 with low density of TK-immunoreactivity). Specimens of transverse (17) and sigmoid colon (20) were obtained from adults undergoing colonic resection for cancer. CCM contractions were measured isotonically and responses to carbachol, neurokinin A (NKA) and electrical field stimulation (EFS) recorded. Carbachol and NKA-evoked contractions in adult and STC colon. Hyoscine (2 micromol L-1) significantly depressed responses to EFS in all preparations. Blockade of NK2 receptors (SR 48968, 2 micromol L-1) significantly depressed EFS-evoked contractions of adult transverse CCM, but had no effect on STC preparations. Thus, neuromuscular transmission in both adults and STC children is predominantly cholinergic and this component is unimpaired in the latter, indicating that reduced TK-immunoreactivity is not a marker for depressed cholinergic responses. Although pharmacologically responsive TK receptors are present in STC colon, we did not detect neuromuscular transmission mediated by release of TKs in these preparations.
authors.affiliation: Murdoch Children's Research Institute and Department of General Surgery, Royal Children's Hospital and Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: M P
authors.initials: MP
authors.lastname: Stanton
authors.forename: P T
authors.initials: PT
authors.lastname: Hengel
authors.forename: B R
authors.initials: BR
authors.lastname: Southwell
authors.forename: C W
authors.initials: CW
authors.lastname: Chow
authors.forename: J
authors.initials: J
authors.lastname: Keck
authors.forename: J M
authors.initials: JM
authors.lastname: Hutson
authors.forename: J C
authors.initials: JC
authors.lastname: Bornstein
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D002217:Carbachol / Q000494:pharmacology; D002648:Child; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology*; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D003248:Constipation / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D015288:Neurokinin A / Q000494:pharmacology; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015320:Tachykinins / Q000494:pharmacology
chemical_list: D018041:Receptors, Neurokinin-2; D015320:Tachykinins; D015288:Neurokinin A; D002217:Carbachol