Signaling via nucleotide receptors in the sympathetic nervous system

Nucleotides have long been recognized as transmitters in the sympathetic nervous system that are involved in both ganglionic and sympatho-effector transmission. In the past 10 years, more than a dozen different receptors for nucleotides have been characterized by molecular cloning. In the same period, a number of stimulatory and inhibitory effects of nucleotides on sympathetic neurons have been identified, and the receptors and signaling cascades involved have been characterized. Within sympathetic ganglia, sympathetic neurons are excited by nucleotides via ATP-gated cation channels (P2X receptors) and via G-protein-coupled nucleotide (P2Y) receptors. At postganglionic sympathetic axons, presynaptic P2X receptors mediate a positive feedback modulation of sympatho-effector transmission, whereas presynaptic P2Y receptors predominantly mediate an autoinhibition of sympathetic transmitter release. This review summarizes the way in which signals generated via these nucleotide receptors are integrated within single sympathetic neurons to contribute to the function of the whole system. The arising knowledge permits predictions about desirable and adverse effects of drugs that bind to these receptors.