Cellular mediators of nitrergic neurotransmission in GI smooth muscles: no easy answer.

Abstract

Gastrointestinal muscles receive both excitatory and inhibitory innervation, and both positive and negative influences impart important regulatory control of motility and transit. Twenty‐five years after nitric oxide (NO) was identified as a key neurotransmitter of enteric inhibitory motor neurons (Bult et al. 1990), the cells mediating nitrergic motor effects and the cellular mechanisms responsible for relaxation remain controversial. Three cell types found within GI muscles, i.e. smooth muscle cells (SMCs), interstitial cells of Cajal (ICC) and PDGFRα+ cells, form an electrical syncytium (the SIP syncytium) that integrates intrinsic and regulatory inputs (Sanders et al. 2014). A recent paper in The Journal of Physiology by Lies and coworkers addresses the question of which cell types mediate nitrergic motor responses in the longitudinal muscle layer of the murine colon (Lies et al. 2015). The authors used cell‐specific, tamoxifen‐inducible expression of Cre recombinase (iCre) in SMCs or ICC bred to mice with floxed Gucy1b3 (Gucy1b3flox/flox) to control expression of β1 subunits of soluble guanylate cyclase (GC), an essential component of NO receptors. The rationale was that elimination of functional receptors in ICC or SMCs would reveal the relative importance of these cells in nitrergic responses.