Detection of a soluble serotonin-binding protein in the mammalian myenteric plexus and other peripheral sites of serotonin storage.

Abstract

Abstract—Groups of neurons intrinsic to the mammalian myenteric plexus have been shown to have both tryptophan hydroxylase and a specific uptake mechanism for serotonin. They are probably serotonergic. A soluble protein with a high binding affinity for serotonin, similar to a protein previously found in rat brain by TAMIR & HUANG (1974), has now been found in the myenteric plexus of both rabbit and guinea pig. Partial purification of the protein from the rabbit's myenteric plexus by ammonium sulfate fractionation increased the ratio of specific to nonspecific serotonin binding almost 3‐fold. Two dissociation constants for serotonin binding were obtained by equilibrium dialysis: 6.7 × 10−10 M and 4.8 × 10−7 M. The protein was similar to the soluble serotonin‐binding protein of CNS: the indole derivatives 5, 6‐ and 5, 7‐dihydroxytryptamine, and 6‐hydroxytryptamine inhibited serotonin binding by 50% at 10−7 M; norepinephrine was a poor inhibitor of serotonin binding; most of the serotonin‐protein complex had a very high molecular weight and did not penetrate a 6.5% acrylamide gel. The appearance of the serotonin binding protein during development of the intestine in fetal rabbit correlates closely with the development of a serotonin uptake mechanism by nerves of this tissue and precedes the ingrowth of the adrenergic innervation. In‐vitro administration of 6‐hydroxydopamine to adult animals has no effect on the binding capacity for serotonin. Binding activity in denervated preparations is only 1/5 that of innervated tissue. It is concluded that the serotonin‐binding protein, which has been found associated with serotonergic pathways in the CNS, is found associated with serotonergic neurons in the periphery as well. Since a similar serotonin‐binding protein is also found in sheep thyroid, which stores but does not take up serotonin, the protein may be a component of the serotonin storage mechanism.