The Nature of Non-Adrenergic Inhibition in the Mammalian Intestine

Abstract

Responses to non-adrenergic inhibitory nerves have been obtained and pharmacologically analysed in isolated intestinal preparations from rabbits, guinea pigs and cats. The nerves were found to differ from adrenergic sympathetic nerves in a number of ways. Their threshold and optimal frequency for electrical stimulation was lower than that of sympathetic nerves and in contrast to sympathetic nerves the peripheral ganglia were situated in or close to the tissue innervated. Responses to non-sympathetic nerves persisted after abolition of sympathetic responses by either adrenergic neurone blocking drugs or by mixtures of α and β adrenoceptor blocking drugs. Non-adrenergic inhibitory responses could be imitated by both nicotine and 5-hydroxytryptamine. Like sympathetic responses the non-adrenergic nerve responses were impaired by reserpine. In the guinea pig isolated colon preparation, it was demonstrated that non-adrenergic nerves have extrinsic connections via the pelvic nerves. A mixture of pempidine and bufotenine abolished responses to pelvic nerve stimulation, suggesting the involvement of both 5-hydroxytryptamine and acetylcholine as ganglionic transmitters. Unsuccessful attempts have been made to isolate and identify the postganglionic transmitter substance from non-adrenergic sympathetic nerves. In addition, a variety of biogenic substances have been examined as potential transmitter substances. Particular attention was paid to the adenine nucleotides in view of recent reports suggesting these as likely transmitter substances in non-adrenergic inhibitory nerves. Little evidence was found to support this concept and it is suggested that the term "purinergic nerves" to describe these nerves is premature. The phenomenon of "rebound contraction" following transmural stimulation of isolated intestinal preparations has been studied. It is suggested that the major part of the response is due to stimulation of cholinergic nerves within the intestinal wall. A short examination has been made of the sympathetic nerve blocking action of β-adrenoceptor blocking substances. The evidence suggests that this action is pre-synaptic but differs from that of guanethidine.