Regionally selective cholinergic stimulation by BRL 24924 in the human isolated gut.
1. The effects of BRL 24924 on cholinergic activity was studied in longitudinal muscle strips obtained from human stomach and colon (taenia). Contractions were evoked by exogenous acetylcholine (ACh) or by electrical field stimulation (EFS) of cholinergic neurones. Inhibitory nerve activity (predominantly non-adrenergic, non-cholinergic; NANC) was detected by measuring the relaxations evoked by EFS in the presence of atropine 1.4 microM. 2. In the stomach, BRL 24924 0.28-28 microM consistently increased the EFS-evoked contractions; lower concentrations (0.0028 and 0.028 microM) increased the contractions in most, but not all of the specimens studied. Since BRL 24924 28 microM did not affect NANC-mediated, EFS-evoked relaxations, and since high concentrations of BRL 24924 (28 and 282 microM) were required to increase ACh-evoked contractions, the increase in EFS-evoked contractions caused by BRL 24924 may be due to a facilitation of ACh release. 3. In the colon, BRL 24924 0.0028-282 microM did not affect EFS-evoked contractions. 4. BRL 24924 may therefore be regionally selective in its ability to stimulate human gastrointestinal cholinergic activity.
Burke
T A
TA
Beecham Pharmaceuticals, Medicinal Research Centre, Harlow, Essex.
Sanger
G J
GJ
D000109:Acetylcholine / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D004064:Digestive System / Q000187:drug effects*; D004558:Electric Stimulation; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C053006:renzapride; D000109:Acetylcholine