The Avian Vasotocin 4 Receptor: its Role in Stress and Homology to the Mammalian Vasopressin 1a Receptor

The chicken VT4R (cVT4R) and human V1aR are regarded as homologous based upon identity of cDNA and amino acid sequences for the receptors of 78% and 69%, respectively. Homology analysis of the cVT4R (NM_001110438) with analogues of other species by NCBI/BLAST show a cDNA and amino acid identity, respectively, of 87%, 87% for the zebra finch V1aR, and 74%, 69% for the rat V1aR. The receptors belong to the Rhodopsin family of G-protein coupled receptors (GPCRs) showing three identical motifs in transmembrane domain 2 (TMD2), boundary of TMD3 and intracellular loop 2, and TMD7.  The two GPCRs also contain conserved sequences shown by neurohypophyseal hormone receptors. Both receptors have been found in brain and pituitary and are involved in stress.  There are, however, marked differences in pituitary and brain distribution of the two receptors in birds and mammals. Specifically the V1aR has been limited to pituitary gonadotropes in mammals (Orcel et al., Endocrinol. 143:4385-88,2002) while the cVT4R occurs in corticotropes (Selvam et al., J. Neuroendocrinol. Jul31.doi 10.111/j1365-2826.2012.02370.x). In the mammalian brain abundance of V1aR occur in neurons located in the lateral septum, diagonal band and lateral hypothalamus all of which affect social behavior.  Those brain areas in chickens display little or no neurons having the VT4R. Regardless of the high sequence identity of a specific receptor among vertebrates, the pattern of distribution in the neuroendocrine system appears different in each class for the V1aR. The unique pattern perhaps enables variable function critical to the stress/social behavioral response of each species.