Belai A, Lefebvre R A, Burnstock G
Department of Anatomy and Embryology, University College London, U.K.
Eur J Pharmacol. 1991 Mar 5;194(2-3):225-34. doi: 10.1016/0014-2999(91)90109-4.
As deficiencies of the cholinergic and non-adrenergic non-cholinergic innervation of the gastrointestinal tract have been described in diabetic rats, we studied the simultaneous release of, and muscular response to, acetylcholine, vasoactive intestinal polypeptide and adenosine-5'-triphosphate in isolated preparations of gastric fundus from control and 8-week streptozotocin-treated diabetic rats. Muscular responses were measured in longitudinal muscle strips prepared from one half of the gastric fundus and release was studied in the other half. The contractile response to acetylcholine and electrical field stimulation was not different in control and diabetic rats. In the presence of atropine, and when tone was increased with prostaglandin F2 alpha, electrical field stimulation, vasoactive intestinal polypeptide and adenosine-5'-triphosphate induced relaxation with a similar response in control and diabetic rats. The basal release of acetylcholine, vasoactive intestinal polypeptide and adenosine-5'-triphosphate was not significantly different in control and diabetic rats. Electrical field stimulation significantly increased the release of the three substances and this increase was tetrodotoxin-sensitive. While the stimulation-induced increase of acetylcholine and vasoactive intestinal polypeptide was not different in control and in diabetic rats, the stimulation-induced release of adenosine-5'-triphosphate increased 3-fold in diabetic compared to control gastric fundus. Desensitization to alpha,beta-methylene adenosine-5'-triphosphate reduced the relaxant response to adenosine-5'-triphosphate and to electrical field stimulation, suggesting a role of adenosine-5'-triphosphate in non-adrenergic non-cholinergic neurotransmission of rat gastric fundus. The reduction of the non-adrenergic non-cholinergic relaxation by alpha,beta-methylene adenosine-5'-triphosphate was greater in diabetic tissues. This, with the increase in stimulation-induced adenosine-5'-triphosphate release, suggests that the purinergic component of the vagal non-adrenergic non-cholinergic response of the stomach may be increased in diabetics.
由于已报道糖尿病大鼠胃肠道存在胆碱能和非肾上腺素能非胆碱能神经支配缺陷，我们研究了对照大鼠和经链脲佐菌素处理8周的糖尿病大鼠胃底离体标本中乙酰胆碱、血管活性肠肽和5'-三磷酸腺苷的同时释放及肌肉反应。肌肉反应在取自胃底一半的纵行肌条中测量，释放则在另一半中研究。对照大鼠和糖尿病大鼠对乙酰胆碱和电场刺激的收缩反应无差异。在阿托品存在的情况下，以及用前列腺素F2α增强张力时，电场刺激、血管活性肠肽和5'-三磷酸腺苷在对照大鼠和糖尿病大鼠中引起的舒张反应相似。对照大鼠和糖尿病大鼠中乙酰胆碱、血管活性肠肽和5'-三磷酸腺苷的基础释放无显著差异。电场刺激显著增加了这三种物质的释放，且这种增加对河豚毒素敏感。虽然对照大鼠和糖尿病大鼠中刺激诱导的乙酰胆碱和血管活性肠肽增加无差异，但与对照胃底相比，糖尿病胃底中刺激诱导的5'-三磷酸腺苷释放增加了3倍。对α,β-亚甲基5'-三磷酸腺苷脱敏降低了对5'-三磷酸腺苷和电场刺激的舒张反应，提示5'-三磷酸腺苷在大鼠胃底非肾上腺素能非胆碱能神经传递中起作用。α,β-亚甲基5'-三磷酸腺苷对糖尿病组织中非肾上腺素能非胆碱能舒张的降低作用更大。这一点，加上刺激诱导的5'-三磷酸腺苷释放增加，提示糖尿病患者胃迷走神经非肾上腺素能非胆碱能反应的嘌呤能成分可能增加。
