Cooke H J, Wang Y Z, Reddix R, Javed N
Department of Physiology, College of Medicine, Ohio State University, Columbus 43210.
Am J Physiol. 1995 Mar;268(3 Pt 1):G465-70. doi: 10.1152/ajpgi.1995.268.3.G465.
Previous studies demonstrated neurally mediated recurrent increases in short-circuit current (Isc) suggestive of anion secretion in guinea pig distal colon. To determine the neural pathways involved, segments of distal colon from guinea pigs were mounted in flux chambers. In muscle-stripped or whole thickness preparations, serosal addition of the histamine H2 receptor agonist, dimaprit, caused cyclical increases in Isc, which were reduced by the chloride channel blocker, N-phenylanthranilic acid, but not by the sodium channel blocker amiloride. Dimaprit stimulated release of [3H]acetylcholine and vasoactive intestinal polypeptide (VIP) from submucosal/mucosal sheets. Dimaprit caused recurrent increases in Isc, which were significantly decreased by mecamylamine, a nicotinic receptor antagonist, and nearly abolished by the muscarinic antagonist, atropine (M3 > M1 = M2). The muscarinic antagonist, 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP, M3 > M1), was more potent than pirenzepine (M1 > M3) in reducing recurrent increases in Isc. Dimaprit- and electrically evoked secretion were inhibited by the VIP antagonists [4Cl-D-Phe6, Leu17]VIP and VIP hybrid. The results suggest the involvement of VIP-ergic and cholinergic neurons utilizing nicotinic and muscarinic synapses in mediating secretion.
先前的研究表明，豚鼠远端结肠中存在神经介导的短路电流（Isc）反复增加，提示有阴离子分泌。为了确定其中涉及的神经通路，将豚鼠远端结肠段安装在通量室中。在肌肉剥离或全层制备中，向浆膜添加组胺H2受体激动剂地马普明会导致Isc周期性增加，这种增加会被氯离子通道阻滞剂N-苯基邻氨基苯甲酸降低，但不会被钠通道阻滞剂氨氯吡咪降低。地马普明刺激了[3H]乙酰胆碱和血管活性肠肽（VIP）从黏膜下层/黏膜片层的释放。地马普明导致Isc反复增加，这种增加被烟碱受体拮抗剂美加明显著降低，被毒蕈碱拮抗剂阿托品（M3>M1 = M2）几乎完全消除。毒蕈碱拮抗剂4-二苯乙酰氧基-N-甲基哌啶甲碘化物（4-DAMP，M3>M1）在降低Isc反复增加方面比哌仑西平（M1>M3）更有效。地马普明和电诱发的分泌受到VIP拮抗剂[4Cl-D-Phe6，Leu17]VIP和VIP杂合体的抑制。结果表明，利用烟碱和毒蕈碱突触的VIP能和胆碱能神经元参与了分泌的介导。
