ABSTRACT

Efferent neurones in the extrinsic parasympathetic and sympathetic outflow from the central nervous system to the large intestine provide the reflex pathways which form and coordinate the motility patterns responsible for the storage, transport and evacuation of the colonic contents. Using experimental models of pelvic nerve and lumbar colonic nerve stimulation we have characterised the effects of selective activation of parasympathetic or sympathetic extrinsic pathways and have defined the neurotransmitters and receptors involved. In summary, we demonstrated that the extrinsic nervous control of the colon involves both prejunctional and direct smooth muscle effects. Efferent fibres to the colon provide cholinergic input to excitatory motoneurones in ganglia of the pelvic and the myenteric plexus, which induce smooth muscle contractions releasing acetylcholine and/or excitatory non-adrenergic, non-cholinergic (NANC) neurotransmitter(s). In addition, efferent parasympathetic fibres within the pelvic nerve may synapse with inhibitory motoneurones inducing muscle relaxation via the release of nitric oxide and/or inhibitory neurotransmitters such as vasoactive intestinal polypeptide and ATP. The relationship between nitric oxide-induced inhibition and a prostaglandin-dependent post-inhibitory excitation in colonic muscles is characteristic for NANC parasympathetic input to the colon. We believe that it plays a role in formation of parasympathetically controlled patterns of colonic activity. It has long been known that parasympathetic motor activity is under sympathetic influence by inhibitory α-adrenoceptors located on cholinergic nerve terminals. However, our observations have demonstrated direct motor responses in the circular muscle of non-sphincteric regions of the colon. Similar to vascular muscle innervation, postganglionic sympathetic fibres in the lumber colonic nerves co-release noradrenaline and ATP and express a presynaptic control mechanism operated by autoinhibitory α2-adrenoceptors. At the level of the muscle, the sympathetic motor response is formed by the activation of different adrenoceptor and purinoceptor subtypes i.e. α-and β-adrenoceptors and P2X receptors.