Structural Diversity in the Catecholamine Transporter Gene Family: Molecular Cloning and Characterization of an L-Epinephrine Transporter from Bullfrog Sympathetic Ganglia

Abstract

Publisher Summary Molecular cloning studies have revealed that distinct gene products encode catecholamine neurotransmitters dopamine (DA) and L-norepinephrine (NE) transporters (DATs and NETs, respectively). Anatomical mapping studies reveal that dopaminergic neurons elaborate DATs, whereas noradrenergic neurons express NETs, though each carrier can efficiently transport both catecholamines. Distinct gene products appear to have been evolved in concert with the structural diversification of the catecholamines themselves. Interestingly, neurons in the rodent brain, which express the enzyme phenylethanolamine-N-methyltransferase (PNMT) and thus are presumed to synthesize epinephrine (Epi) from NE, exhibit little or no expression of DAT or NET. These findings suggest that synapses formed by PNMT-positive neurons either do not require rapid clearance to carry out efficient chemical signaling or elaborate a molecularly distinct transporter. In this regard, Episynthesizing neurons in amphibians have been reported to express catecholamine transporters with a pharmacology similar to that displayed by NET, though a specific carrier has yet to be isolated and characterized. For this purpose mRNA is isolated and a cDNA library is prepared from sympathetic ganglia of the bullfrog, Ram catesbtuna . This study resulted in identification of frog ET (fET), an amphibian catecholamine transporter with enhanced efficiency for L-Epi transport, that reveals an evolutionary path for divergence between NETs and ETs and raises the question of whether the two transporters coexist in a single species.