Appropriate experimental approach is critical for identifying neurotransmitter substances: application to enteric purinergic neurotransmission

摘要

to the editor: The identity of the purinergic neurotransmitter in the gastrointestinal (GI) tract is a controversial issue (12). For several decades adenosine 5'-triphosphate (ATP) was assumed to be the enteric inhibitory purinergic neurotransmitter (1-3). However, recent studies have shown that beta-nicotin-amide adenine dinucleotide (P-NAD), ADP-ribose, and uridine adenosine tetraphosphate (Up4A) satisfy both pre- and postjunctional requirements for a neurotransmitter in GI muscles of human, monkey, and mouse better than ATP (4, 5, 10, 13). The study by Wang et al. (14) investigated whether beta-NAD might be a neurotransmitter in the enteric nervous system (ENS) or a prejunctional modulator of neurotransmitter release in muscles of guinea pig small intestine and colon and human jejunum. We believe that there are errors in the interpretation of the data in this study resulting from the experimental approach. In this study, beta-NAD was applied to solutions bathing muscles in organ baths. Applied in this manner, beta-NAD did not affect membrane potentials in smooth muscles of guinea pig colon or human jejunum. However, beta-NAD suppressed inhibitory junction potentials (IJPs) and the contractile responses to nerve stimulation. The latter effect was inhibited by an adenosine A1 receptor antagonist, 8-cyclopen-tyl-1,3-dipropylxanthine. From these observations the authors concluded that "the results do not support an inhibitory neurotransmitter role for beta-NAD at intestinal neuromuscular junctions." Instead, the authors suggested that "beta-NAD is a ligand for adenosine A1 receptors expressed by enteric neurons."