Neural regulation of intestinal smooth muscle growth in vitro

The loss of intrinsic neurons is an early event in inflammation of the rat intestine that precedes the growth of intestinal smooth muscle cells (ISMC) . To study this relationship, we cocultured ISMC and myenteric plexus neuro ns from the rat small intestine and examined the effect of scorpion venom, a selective neurotoxin, on ISMC growth. By 5 days after neuronal ablation, ISMC number increased to 141 +/- 13% (n = 6) and the uptake of [H-3]thymidi ne in response to mitogenic stimulation was nearly doubled. Atropine caused a dose-dependent increase in [H-3]thymidine uptake in cocultures, suggesti ng the involvement of neural stimulation of cholinergic receptors in regula tion of ISMC growth. In contrast, coculture of ISMC with sympathetic neuron s increased [H-3]thymidine uptake by 45-80%, which was sensitive to propran olol (30 mu M) and was lost when the neurons were separated from ISMC by a permeable filter. Western blotting showed that coculture with myenteric neu rons increased alpha-smooth muscle-specific actin nearly threefold to a lev el close to ISMC in vivo. Therefore, factors derived from enteric neurons m aintain the phenotype of ISMC through suppression of the growth response, w hereas catecholamines released by neurons extrinsic to the intestine may st imulate their growth. Thus inflammation-induced damage to intestinal innerv ation may initiate or modulate ISMC hyperplasia.