Cerebellin-like peptide: tissue distribution in rat and guinea-pig and its release from rat cerebellum, hypothalamus and cerebellar synaptosomes in vitro.

We have developed a specific radioimmunoassay for "cerebellin", a 16-amino acid peptide recently isolated from rat cerebellum. In both rat and guinea-pig, cerebellin-like immunoreactivity was highest in the cerebellum but was also present in high concentrations elsewhere in the central nervous system, especially in the hypothalamus. In both species, cerebellin-like immunoreactivity was found in other organs (heart, kidney and stomach) and at lower concentrations in the gastrointestinal tract. In the brain of both species, cerebellin-like immunoreactivity consisted of a single molecular form with an elution position on gel filtration and high-performance liquid chromatography identical to that of synthetic rat cerebellin. However, peripheral tissue contained an additional immunoreactive peak of higher molecular weight. Cerebellin was concentrated in synaptosomal preparations of rat brain, and its subcellular distribution pattern in rat brain was identical to that of two other known synaptosomal peptides, vasoactive intestinal polypeptide and substance P. Studies with superfused cerebellar synaptosomes and slices of rat cerebellum and hypothalamus demonstrated calcium-dependent cerebellin release when stimulated by high potassium concentrations as well as the addition of the calcium ionophore A23187. Cerebellin has therefore a widespread distribution and fulfils two criteria for a neurotransmitter, in that it is found in brain synaptosomes and shows calcium dependent, depolarization-induced release from nervous tissues and isolated nerve endings. It may, therefore, be a component of a novel neurotransmitter system.