Glutamate Decarboxylases in Nonneural Cells of Rat Testis and Oviduct: Differential Expression of GAD₆₅ and GAD₆₇

Abstract

gamma-Aminobutyric acid (GABA) and its synthetic enzyme, glutamate decarboxylase (GAD), are not limited to the nervous system but are also found in nonneural tissues. The mammalian brain contains at least two forms of GAD (GAD67 and GAD65), which differ from each other in size, sequence, immunoreactivity, and their interaction with the cofactor pyridoxal 5'-phosphate (PLP). We used cDNAs and antibodies specific to GAD65 and GAD67 to study the molecular identity of GADs in peripheral tissues. We detected GAD and GAD mRNAs in rat oviduct and testis. In oviduct, the size of GAD, its response to PLP, its immunoreactivity, and its hybridization to specific RNA and DNA probes all indicate the specific expression of the GAD65 gene. In contrast, rat testis expresses the GAD67 gene. The GAD in these two reproductive tissues is not in neurons but in nonneural cells. The localization of brain GAD and GAD mRNAs in the mucosal epithelial cells of the oviduct and in spermatocytes and spermatids of the testis shows that GAD is not limited to neurons and that GABA may have functions other than neurotransmission.

Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene.

“…GAD activity and immunoreactivity are also present in nonneural tissues, including pancreatic islets, testis, and oviduct (2,38,(39)(40)(41)(42). Testis, for example, contains immunoreactive GAD67 as well as GAD67 mRNA (32,40).…”

“…Testis, for example, contains immunoreactive GAD67 as well as GAD67 mRNA (32,40). But the GAD67 mRNAs in the testis have multiple sizes, all different from the 3.7-kb brain mRNA, and presumably derived from the single GAD67 gene by alternative splicing or alternative polyadenylylation (40,42). The oviduct, like the testis, contains multiple GAD mRNAs, but these derive principally from the GAD65 gene (40,42).…”

“…But the GAD67 mRNAs in the testis have multiple sizes, all different from the 3.7-kb brain mRNA, and presumably derived from the single GAD67 gene by alternative splicing or alternative polyadenylylation (40,42). The oviduct, like the testis, contains multiple GAD mRNAs, but these derive principally from the GAD65 gene (40,42). Direct evidence for alternative splicing of a GAD67 transcript, however, is thus far available only in the developing rat brain, where alternative splicing A.…”

Transient expression of glutamate decarboxylase and γ‐amino butyric acid in embryonic lens fibers of the rat

“…The transient appearance of GAD67 and GABA in the spinal cord coincides with active growth and may relate to trophic, metabolic, or specific differentiation roles (Ma et al, 1992;Behar et al, 1993). Indeed, although GABA is an inhibitory neurotransmitter in the mature nervous system, it is also found in many other tissues where its functions have not been resolved (Erdo and Wolff, 1990;Persson et al, 1990;Gilon et al, 1991;Tillakaratne et al, 1992;Faulkner-Jones et al, 1993). It is noteworthy that GABA was detected at much higher concentrations in 1-to 3-year-old monkey lenses than in 7-week-old rat or adult cat lenses (Reddy, 1967).…”

“…Although the GADS are expressed predominantly in the central nervous system (CNS), where their product, GABA, acts in the well-differentiated CNS as an inhibitory neurotransmitter (Roberts, 19761, GABA and GAD are also present in numerous non-neuronal tissues, suggesting that they are utilized for multiple functions (Seiler and Lajtha, 1987;Erdo and Wolff, 1990;Persson et al, 1990;Gilon et al, 1991;Tillakaratne et al, 1992;Faulkner-Jones et al, 1993). Increasing evidence indicates that GABA may act as a morphogen in developing neuronal, as well as non-neuronal cells (see Lauder, 1993).…”