Tetrodotoxin-sensitive and -insensitive relaxations in the rat oesophageal tunica muscularis mucosae.

1. Relaxation responses were produced by vagal and field stimulation, respectively, of the whole oesophagus preparation from the rat and of the isolated tunica muscularis mucosae (t.m.m.) preparation from the rat. These relaxation responses persisted in the presence of antagonists of histamine, serotonin, noradrenaline and acetylcholine. 2. Unlike vagally evoked relaxation, that evoked by low-frequency field stimulation, i.e. field-stimulated relaxation (f.s.r.) was generally resistant to tetrodotoxin (TTX). 3. Both types of relaxations exhibited remarkable temperature sensitivity and were abolished by lowering the bath temperature from 37 to 28 degrees C. 4. TTX-resistant relaxations were also produced by scorpion (Leiurus quinquestriatus) venom, the calcium ionophore, A23187 (calimycin) and by increasing the extracellular potassium by 2 mM. The failure of these agents to inhibit f.s.r. is inconsistent with a releasing and/or depleting action on any endogenous mediator. 5. Relaxations produced by vasoactive intestinal peptide (VIP) could be blocked by alpha-chymotrypsin which, however, failed to abolish f.s.r., suggesting that VIP is not the mediator of f.s.r. 6. F.s.r. was completely blocked by the calcium channel antagonists, verapamil (10(-6) M), nifedipine (10(-7) M), and by magnesium (20 mM). 7. Our results indicate that TTX-insensitive relaxations in the isolated t.m.m. are dependent upon extracellular calcium, are due to activation of potential-operated calcium channels and are not mediated by VIP.