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 a and 8B
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 nonadrenergic
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 B-adrenoceptor blocking substances.
The evidence suggests that this action is pre-synaptic but
differs from that of guanethidine.

Date of Award	1973
Original language	English