BRL 24924对人离体肠道的区域选择性胆碱能刺激作用。

Regionally selective cholinergic stimulation by BRL 24924 in the human isolated gut.

Burke T A, Sanger G J

Beecham Pharmaceuticals, Medicinal Research Centre, Harlow, Essex.

Br J Clin Pharmacol. 1988 Sep;26(3):261-5. doi: 10.1111/j.1365-2125.1988.tb05275.x.

Abstract

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.

摘要

研究了BRL 24924对取自人胃和结肠（结肠带）的纵行肌条胆碱能活性的影响。收缩由外源性乙酰胆碱（ACh）或胆碱能神经元的电场刺激（EFS）诱发。通过在1.4微摩尔阿托品存在下测量EFS诱发的舒张来检测抑制性神经活性（主要是非肾上腺素能、非胆碱能；NANC）。2. 在胃中，0.28 - 28微摩尔的BRL 24924持续增加EFS诱发的收缩；较低浓度（0.0028和0.028微摩尔）在大多数但并非所有研究的标本中增加了收缩。由于28微摩尔的BRL 24924不影响NANC介导的、EFS诱发的舒张，并且由于需要高浓度的BRL 24924（28和282微摩尔）来增加ACh诱发的收缩，BRL 24924引起的EFS诱发收缩的增加可能是由于促进了ACh的释放。3. 在结肠中，0.0028 - 282微摩尔的BRL 24924不影响EFS诱发的收缩。4. 因此，BRL 24924在刺激人胃肠胆碱能活性的能力上可能具有区域选择性。