Mammalian endothelin (ET) receptors, termed ET_AR and ET_BR, are derived from two intron-containing genes and the functional splice variants of ET_BR but not ET_AR have been identified. Here, we report about the isolation of cDNAs of ET_AR transcripts from rat anterior pituitary, which are generated by alternative RNA splicing. Deletion of exon 2 and insertion of fragments from intron 1 and 2 accounted for formation of three misplaced proteins, whereas the insertion of a fragment from intron 6 resulted in generation of a functional plasma membrane receptor, termed ET_AR-C13. In this splice variant, the C-terminal 382S-426N sequence of ET_AR was substituted with a shorter 382A-399L sequence, resulting in alteration of the putative domains responsible for coupling to G_q/11 and G_s proteins and the endocytotic recycling, as well as in deletion of the predicted protein kinase C/casein kinase 2 phosphorylation sites. The mRNA transcripts for ET_AR-C13 were identified in normal and immortalized pituitary cells and several other tissues. The pharmacological profiles of recombinant ET_AR and ET_AR-C13 were highly comparable, but the coupling of ET_AR-C13 to the calcium-mobilizing signaling pathway was attenuated, causing a rightward shift in the potency for agonist. Furthermore, the efficacy of ET_AR-C13 to stimulate adenylyl cyclase signaling pathway and to internalize was significantly reduced. These results indicate for the first time the presence of a novel ET_A splice receptor, which could contribute to the functional heterogeneity among secretory pituitary cell types.