Transmitter interactions in the rabbit internal anal sphincter. Knudsen, M. A., E. B. Glavind, A. Tottrup. Dept. of Surgical Research 900, University Hospital of Aarhus, Section Amtssygehuset, DK-8000 Aarhus, Denmark
APStracts 2:0068G, 1995.
The aim of the present study was to investigate the relative importance of the different putative NANC mediators and their interplay with cholinergic nerves in the rabbit internal anal sphincter (IAS). IAS preparations were mounted in organ baths for recording of isometric tension. Transmural field stimulation (TMS; 5s trains, supramax. voltage (140-160 V, 0.4 ms impulse duration) was applied every 2 min with frequencies varying from 0.2-32 Hz. TMS induced frequency-dependent relaxations that amounted to 89.3+/-2.2% (N=7). N_-nitro-L-arginine (L-NNA, 10-7-10-4 M, 8 Hz) reduced relaxations and this effect was partially inhibited by preincubation with L-arginine (10-4 M). The effect of L-NNA was attenuated by atropine preincubation. Apamin (10-6 M) shifted the frequency -response curve to the right, but left maximal relaxations in response to TMS unaffected. In the presence of L-NNA (10-4 M) and atropine (10-6 M), the action (area between the frequency-response curve with or without a substance) of apamin was more pronounced, but despite the presence of both L-NNA and apamin some relaxation still remained. The frequency-response curve (control) was significantly shifted to the right by carbachol (10-6 M). Concentration-response experiments showed that the response to exogenous NO (10-7-10-4 M) was unaffected by carbachol (10-6 M) preincubation, while responses to VIP and ATP were significantly reduced. Apamin almost abolished responses to ATP (10-4 and 10-3 M), while VIP- (10-10-10-6 M) and NO-(10-7-10-4 M) induced relaxations were unaffected. L-NNA had no effect on relaxations induced by VIP, NO and ATP. The results suggest that the rabbit internal anal sphincter is innervated by cholinergic excitatory nerves and by NANC inhibitory nerves. The NANC nerves involve at least 3 different transmitters: NO, an apamin-sensitive mediator (possibly ATP) and a non-L-NNA, non-apamin sensitive agent. A complex interaction possibly involving both pre- and postjunctional mechanisms seems to exist between these systems. 

Received 5 July 1994; accepted in final form 24 February 1995.
APS Manuscript Number G257-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 April 1995.