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

Abstract

SUMMARY1. 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 a-and /J-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.

Development of cholinergic nerve transmission in the chick oesophagus

“…These observations suggest that the intrinsic cholinergic nerve starts to function in the chick oesophagus as early as 10 days of incubation. The early appearance of functional cholinergic innervation to the smooth muscles of the chick oesophagus is consistent with the observation in the rabbit ileum (Gershon & Thompson, 1973), rat ileum (Miyazaki et al, 1982) and rat stomach (Ito et al, 1988). The C6-and atropine-sensitive response elicited by vagal nerve stimulation in the chick oesophagus appeared a day later than that induced by transmural nerve stimulation, suggesting that the oesophagus could accept the input from the vagus nerve at 11 days of incubation and that ganglionic transmission also develops immediately after neuro-effector transmission is established.…”

“…which the response to nerve stimulation appears, both the nerve elements and the smooth muscle cells were observed to be morphologically immature (Gershon & Thompson, 1973). Morphological studies on the enteric nervous system indicated that the maturation of ganglion cells and synapses occurs slowly during the embryonic period (Bennett & Cobb, 1969;Daikoku et al, 1975;Gershon et al, 1981;Lolova, 1983a, b), sug-gesting that quantitative and qualitative changes in functional innervation may also take place during this period.…”

“…It was into many types of neurones in the gut wall reported that these neurones begin to function in (cholinergic: Le Douarin, 1980;5-hydroxy-sequential manner and that the intrinsic neurone tryptaminergic : Epstein et al, 1980; peptidergic: which functions first is cholinergic and excitatory in Epstein et al, 1983). The functional significance of nature (Gershon & Thompson, 1973;Miyazaki et al, 1982;Ito et al, 1988). In the earliest stage at Author for correspondence.…”

Development of Motor Response to Intramural Nerve Stimulation and to Drugs in Rat Small Intestine

“…This is consistent with reports that the reactivity to transmitters precedes the functional innervation in rat vas deferens (Swedin, 1972) and chick heart (Pappano, 1977). However, in the rabbit intestine, the response to exogenous ACh appeared simultaneously with the onset of functional cholinergic innervation (Gershon & Thompson, 1973). There could be species differences.…”

“…It has been reported that stimulation of the intramural inhibitory neurones (non-adrenergic) in the gut caused the aftercontraction with (Holman & Hughes, 1965;Bennett, 1966) or without (Gershon & Thompson, 1973) preceding relaxation. Furthermore, it has also been observed that a non-cholinergic excitatory neurone causes an atropine-resistant contraction in avian and mammalian gastro-intestinal tracts (Ambache & Freeman, 1968;Nakazato, Sato & Ohga, 1970;Takewaki & Ohashi, 1977).…”