Effects of endothelin-1 on the isolated guinea-pig ileum: role of Na+ ions

Abstract

Endothelin-1 induced a unusual transient biphasic effect (relaxation followed by contraction) in the isolated guinea-pig ileum. The contractile component of the response was concentration-dependent in the dose range studied, but the relaxant component was not. Neuronal mechanisms and cyclic GMP do not seem to be involved in the relaxing effect since this component was not affected by either tetrodotoxin, atropine or methylene blue. Endothelin-1 induced desensitization which was well characterized for the contractile component of the response, and was only partially reversed after a 3-h resting period. The effects of endothelin-1 were particularly sensitive to decreases in the Na+ gradient induced either by lowering the Na+ concentration in the medium or by treating the tissue with ouabain or by a previous treatment with acetylcholine. Amiloride partially inhibited the response induced by endothelin-1 indicating that Na+ channels and/or Na+/H+ exchange are probably involved in its action. Our results suggest that the contractile response induced by endothelin-1 in the isolated guinea-pig ileum depends greatly on Na+ ions, in contrast to the responses observed in vascular smooth muscle.

Endothelin (16–21): biphasic effect and no desensitization on the guinea‐pig isolated ileum

“…Isometric recordings showed that in low-Na+ (80 mM) medium both components of the response induced by endothelin (16-21) were greatly reduced (Figure 4) as was previously observed with endothelin-I (Figure 4; Miasiro & Paiva, 1990) and endothelin-3 (Miasiro & Paiva, 1992). Effect of endothelin (16-21) on tissues desensitized to endothelin-J and endothelin-3…”

“…However, repeated application of endothelin (16-21) did not induce desensitization of the preparation, in contrast to the desensitization induced by endothelin-I and endothelin-3, which was not reversed even after a 3 h resting period (Miasiro & Paiva, 1990;1992). This suggests that endothelin (16-21) might interact with some site other than the endothelin receptor, which would give rise to an endothelin-like response in the guinea-pig ileum.…”

“…We have previously observed that endothelin-I and endothelin-3 induce specific desensitization of the guinea-pig ileum (Miasiro & Paiva, 1990;1992). By studying cross-tachyphylaxis between these two isopeptides, it was concluded that there are at least two subtypes of endothelin receptors in the guinea-pig ileum: one selective for endothelin-1 and another one which is non-selective (Miasiro & Paiva, 1992).…”

“…In this tissue, the responses to endothelin-1 and endothelin-3 were characterized by a homologous desensitization (tachyphylaxis), and were markedly dependent on the Na+ gradient across the smooth muscle cell membrane (Miasiro & Paiva, 1990;1992). Wollberg et al (1991) have also reported a relaxant component in the response of the guinea-pig to endothelins and observed evidence for desensitization, but did not investigate this property further.…”

“…We have investigated the effect of endothelin-1 (Miasiro & Paiva, 1990) and endothelin-3 (Miasiro & Paiva, 1992) on the guinea-pig ileum and observed that both peptides induced a direct biphasic effect (relaxation followed by contraction). In this tissue, the responses to endothelin-1 and endothelin-3 were characterized by a homologous desensitization (tachyphylaxis), and were markedly dependent on the Na+ gradient across the smooth muscle cell membrane (Miasiro & Paiva, 1990;1992).…”