Actions of somatostatin on excitatory and inhibitory nerves in the intestine

Isolated segments from the guinea-pig ileum and colon were used to investigate the sites of action of somatostatin on intestinal nerves and muscle. Somatostatin reduced the amplitude of the contraction caused by stimulation of cholinergic nerves in the ileum, without antagonizing receptors for acetylcholine on the muscle, which indicates that somatostatin inhibits the release of transmitter from the cholinergic nerves. Somatostatin caused the intestinal muscle to relax. The relaxation was blocked by tetrodotoxin but not by guanethidine, indicating that somatostatin stimulates enteric non-adrenergic inhibitory nerves. The threshold of concentration for these actions of somatostatin was low (2 to 6 × 10^-10 M). At higher concentrations, somatostatin caused a transient inhibition of peristaltic reflexes and it also stimulated cholinergic nerves. No evidence was obtained for a direct action of somatostatin on intestinal muscle. It is concluded that somatostatin is possibly a neurotransmitter in the intestine that is released at neuro-neuronal junctions and causes an inhibition of intestinal movements.