The maturation of neuromuscular function in a multiply innervated structure: development of the longitudinal smooth muscle of the foetal mammalian gut and its cholinergic excitatory, adrenergic inhibitory, and non-adrenergic inhibitory innervation.

1. The earliest components of the developing innervation of the rabbit intestine to be detected in this study were the cholinergic excitatory and the intrinsic inhibitory innervation. These developed simultaneously in the rabbit at 17 days of gestation. Both were also present in the mouse by the 16th day of gestation. Responsiveness of rabbit tissue to exogenous acetylcholine appeared together with the advent of a functional cholinergic innervation. Since excitatory responses were potentiated by eserine, the tissue was probably able to inactivate acetylcholine through hydrolysis mediated by cholinesterase. Early relaxant responses resisted blockade by adrenergic neurone blocking agents and by antagonists active at alpha- and beta-adrenoceptors.2. The development of the adrenergic innervation lagged far behind that of the other two components. Specific uptake of noradrenaline in the rabbit was detected for the first time at the 21st day of gestation and stores of noradrenaline could not be detected histochemically until 26-28 days. However, relaxant responses to stimulation of the perivascular sympathetic supply, such as characterize adult tissues, had not yet developed by the time of birth. Relaxation in response to perivascular stimulation could be seen 30 days after birth.3. Morphologic studies indicated that the longitudinal layer of smooth muscle was very primitive when an effective innervation was established. Although contractile, the cells were still myoblasts. Neural elements also appeared primitive. Thus considerable morphological maturation follows the development both of a functioning contractile machinery and innervation in the foetal gut.4. This study helps establish that the intrinsic inhibitory innervation of the gut is not adrenergic.