Endothelin receptors in human and guinea-pig gallbladder muscle

We measured contraction of muscle strips caused by endothelin (ET) isopeptides and binding of ¹²⁵I-ET-1 to muscle cell membranes prepared from human and guinea-pig gallbladders. Visualization of ¹²⁵I-ET-1 binding sites in tissue was performed by autoradiography. Results in human were similar to those in guinea-pig. ET-1 caused tetrodotoxin and atropine-insensitive contraction. The relative potencies for ET isopeptides to cause contraction were ET-1 = ET-2 > ET-3. ET-1 caused contraction was only slightly inhibited by BQ-123 (potent ET_A receptor antagonist) and not by BQ-788 (potent ET_B receptor antagonist). It was inhibited by the combination of both. Autoradiography localized ¹²⁵I-ET-1 binding to the smooth muscle layer. Binding of ¹²⁵I-ET-1 to muscle cell membranes was saturable and specific. Analysis of dose-inhibition curves demonstrated the presence of two classes of receptors. One class (ET_A receptor) had a high affinity for ET-1 and ET-2 but a low affinity for ET-3, and the other (ET_B receptor) a high affinity for ET-1, ET-2 and ET-3. These results demonstrate that similar to guinea-pig, human gallbladder possesses both ET_A and ET_B receptors cooperating to mediate muscle contraction.