Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paralytic ileus is defined as an inhibition of propulsive intestinal motility. Postoperative ileus is the most common type, however, also during sepsis and critical illness paralytic ileus is a common finding. The pathogenesis of paralytic ileus is still debated. It is believed to result from the activation of inhibitory neural reflex pathways and activation of inflammatory processes. It is generally accepted that postoperative ileus results from the activation of an inhibitory neural reflex pathway. In our rat model we showed that different degrees of nociceptive stimulation activate different reflex pathways: laparatomy activates an adrenergic inhibitory reflex pathway, whereas manipulation results in additional activation of inhibitory NANC neurons releasing NO and VIP as neurotransmitters. We also demonstrated that blockade of the afferent limb of the reflex pathway by peripheral kappa-opioid agonists or by non-steroidal anti-inflammatory drugs ameliorated postoperative ileus. However, the use of prokinetics lead to disappointing results. In the murine septic model we demonstrated an important role for activation of inducible NO synthase in the endotoxin-induced delay in gastric emptying and small intestinal transit. We hypothesise that activation of the residential macrophages in the gut wall leads to the production of iNOS and other inflammatory mediators. These mediators will attract more inflammatory cells and influence smooth muscle contractility. Next, we provide evidence that production of iNOS results in the activation of guanylyl cyclase leading to the production of cGMP and smooth muscle relaxation. However, a parallel mechanism of action for NO via oxidative stress needs further investigation.
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PMID:Study of the pathogenesis of paralytic ileus in animal models of experimentally induced postoperative and septic ileus. 1467 47