Local modulation of intestinal ion transport by enteric neurons

Principles of autonomic nervous system control of intestinal ion transport need to include the newer concepts of the enteric nervous system (ENS). Based on studies of nervous control of the myenteric plexus, it is likely that ENS control of intestinal transport occurs through local mechanisms. In vitro transport studies and a limited number of radioreceptor-binding studies in mucosal cells support the notion that putative neurotransmitters alter transport by acting directly with mucosal receptors. In vivo and in vitro studies cannot alone uncover the indirect transport effects that neurotransmitters may have when they interact with enteric neurons. Studies focused on uptake and release of neurotransmitters suggest that norepinephrine (NE)-induced absorption may be modulated by local NE presynaptic neuronal mechanisms. Endogenous NE release may be enhanced by nicotinic and angiotensin II agents but decreased by muscarinic and alpha-adrenergic agents or prostaglandins. Presynaptic neuronal mechanisms that modulate endogenous acetylcholine (ACh) release and ACh-induced secretion are less well defined. Intestinal transport may be controlled by negative feedback, interneuronal, or transsynaptic presynaptic mechanisms. We propose that transport is controlled by a balance between the principal neurotransmitters NE and ACh. These neurotransmitters may be modulated by neuroactive peptides located either in neurons or in enteroendocrine cells. Efferent neurons may modulate release of neuropeptides from enteroendocrine cells into the luminal or antiluminal sides of mucosal cells. Intestinal transport also may be controlled by luminal factors that cause neuropeptide release from enteroendocrine cells or by specialized luminal receptors acting on sensory afferent neurons and intrinsic neuronal reflexes. Therefore, local modulation of intestinal transport by the ENS represents a finely tuned neuronal system with complex interrelations similar to many found in the central nervous system.