α-Latrotoxin-induced transmitter release in feline oesophageal smooth muscle: focus on nitric oxide and vasoactive intestinal peptide

Abstract

1. The effects of α-latrotoxin (αLTX) on muscle tone, resting membrane potential, cyclic nucleotide content, and ultrastructure were examined in feline oesophageal smooth muscle, including the lower oesophageal sphincter (LOS).

2. In circular smooth muscle strips from LOS developing active tone, αLTX (1 nM) induced a 94±3% (n=16) relaxation. Intermittent treatment with αLTX for 4 h abolished the response. Pretreatment with N^G-nitro-L-arginine (L-NOARG; 0.1 mM) attenuated the relaxation.

3. In carbachol-contracted circular smooth muscle strips from the LOS and oesophageal body (OB), αLTX induced a 95±5% (n=6) and 73±9% (n=8) relaxation, respectively. The relaxations were attenuated by L-NOARG, and in LOS strips, the relaxation was abolished by the combination of L-NOARG and vasoactive intestinal peptide (VIP)-antiserum (1:25). At resting tension in circular smooth muscle strips from the OB, αLTX induced a scopolamine sensitive contraction in the presence of L-NOARG.

4. In circular LOS and OB preparations, αLTX changed the resting membrane potential from −49±2 mV to −59±3 mV (n=4), and −62±2 mV to −71±3 mV (n=4), respectively.

5. The αLTX-induced relaxation of LOS and OB muscle was associated with a 138% and 72% increase in cyclic GMP levels, respectively. No changes in cyclic AMP levels were observed.

6. Ultrastructural analysis of LOS and OB revealed a rich supply of nerve profiles containing small synaptic and large dense core vesicles. αLTX treatment resulted in a loss of both types of vesicle.

7. These results suggest that αLTX induces relaxation of oesophageal circular smooth muscle associated with NO-generation and transmitter release from synaptic vesicles. Beside NO, VIP seems to be involved in the relaxant effects of αLTX on the LOS. In addition, αLTX may have contractile effects by release of acetylcholine.

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