Cell-specific Deletion of Nitric Oxide-Sensitive Guanylyl Cyclase Reveals a Dual Pathway for Nitrergic Neuromuscular Transmission in the Murine Fundus

摘要: Background & Aims It is not clear how nitric oxide (NO) released from enteric neurons relaxes gastrointestinal (GI) smooth muscle. In analogy to the vascular system, NO might directly induce relaxation of muscle cells (SMCs) by acting on its receptor, NO-sensitive guanylyl cyclase (NO-GC). Alternatively, intermediate cells, such as interstitial Cajal (ICCs), detect nitrergic signals indirectly regulate tone, and thereby motor function GI tract. We investigated role ICCs SMCs in using mice with cell-specific disruption gene encoding β 1 subunit NO-GC ( GUCY1B3 ). Methods created that lack specifically (SM-guanylyl knockout [GCKO]), (ICC-GCKO), or both (SM/ICC-GCKO). effects exogenous endogenous murine fundus isometric force studies. Total gut transit time was measured monitor functional consequences deletion motility in vivo. Results expressed ICC SMC. Deletion receptor incompletely reduced NO-induced relaxation, which hardly affected after ICC-specific deletion. Gut did change SM-GCKO ICC-GCKO compared control mice. However, observed SM/ICC-GCKO mice, had increased controls. Conclusions only relax fundus; combination blocks signaling. Therefore, jointly mediate relaxant effect NO.