PEC-60 and related peptides as hormones in the gastrointestinal tract and the immune system and as generalized cotransmitters in catecholamine neurons

The present and previous research has given evidence that PEC-60 may represent a hormone like peptide in the gastrointestinal tract and in the immune system, being formed and released from goblet cells of the gastrointestinal tract and from monocytes within the immune system. A most interesting finding is the demonstration of a PEC-60-like immunoreactivity within the vast majority of central and peripheral catecholamine (CA) neurons. The analysis of the effects of centrally administered PEC-60 on regional CA utilization and levels suggests that PEC-60 can induce regionally selective reductions of CA levels and of CA utilization in the striatum, nucleus accumbens, the olfactory tubercle and the hypothalamus, including the median eminence. PEC-60 given centrally may also have substantial. effects on pre- and postsynaptic dopamine (DA) mechanisms in view of the ability of PEC-60 in vitro in the low nanomolar range to reduce the affinity of D2 receptors as well as to increase the proportion of D2 receptors in the high affinity state acting on a putative 'PEC-60' receptor. Intrastriatally perfused PEC-60 (100 nM) increases DA release. Striatal GABA release, which is increased by D1 mechanisms, is unaffected as is the binding characteristics of D1 receptors. These results may indicate reduction of D2 receptor mediated striatal DA transmission after 'PEC-60' receptor activation. All these results taken together suggest a generalized cotransmitter role of PEC-60-like peptides in central CA neurons.