title: Effects of erythromycin on human colonic circular muscle in idiopathic chronic constipation.
abstract: BACKGROUND
  Erythromycin has been shown to have profound prokinetic effects on the gastrointestinal tract of humans and animals, probably through its action on endogenous motilin receptors. The purpose of this study was to determine both the direct and indirect effects ('off contraction') of erythromycin and motilin on ex vivo circular muscle strips of the distal colon from patients with or without idiopathic chronic constipation (ICC).
  
  
  METHODS
  Cumulative concentrations of erythromycin (1-20 microM) and motilin (0.05-1 microM) were tested in both control and ICC preparations in order to evaluate the direct drugs effect. A range doses of both erythromycin (0.5-10 microM) and motilin (0.05-0.5 microM) were tested on their ability to affect the off-contraction that follows the typical inhibitory response evoked by low frequencies of Electrical Field Stimulation (EFS) (1-5 Hz, 20 V, 1 msec pulse trains lasting 1 min).
  
  
  RESULTS
  The direct effect of both erythromycin and motilin was a slight increase (less than 10% of the maximal ACh-induced contraction) in the basal tension, with no dose-response relationship. The off-contraction, evoked by EFS, was not affected by drugs pretreament in control preparations. Conversely, in ICC preparations both drugs significantly increased the off-contraction (about 30%).
  
  
  CONCLUSIONS
  Erythromycin causes mainly an indirect contractile effect in circular muscle strips from ICC patients. This effect may be related to the activation of inhibitory neuronal motilin receptors. This activation might potentiate NANC relaxation, proportionally increasing the circumferential reflex contraction that follows the EFS-induced relaxation.
authors.affiliation: Medical School, University of Bari, Italy. chieppa@farmacol.uniba.it
authors.forename: D M
authors.initials: DM
authors.lastname: Chieppa
authors.forename: G
authors.initials: G
authors.lastname: Mansi
authors.forename: R
authors.initials: R
authors.lastname: Rinaldi
authors.forename: M
authors.initials: M
authors.lastname: Serio
authors.forename: C
authors.initials: C
authors.lastname: Nacci
authors.forename: M
authors.initials: M
authors.lastname: Montagnani
authors.forename: M A
authors.initials: MA
authors.lastname: Potenza
authors.forename: M A
authors.initials: MA
authors.lastname: De Salvia
authors.forename: C I
authors.initials: CI
authors.lastname: Mitolo
authors.forename: M
authors.initials: M
authors.lastname: Rinaldi
authors.forename: D F
authors.initials: DF
authors.lastname: Altomare
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002908:Chronic Disease; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D003248:Constipation / Q000188:drug therapy* / Q000503:physiopathology; D004917:Erythromycin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009037:Motilin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D009037:Motilin; D004917:Erythromycin