The pineal gland in mammals is an endocrine organ and generally does n
ot exhibit neuronal characteristics. However, it is known that under c
ulture conditions, cells from newborn rat pineals express properties c
haracteristic of photoreceptors. Here, we studied the potential of rat
pineal cells to differentiate into neuronal cell types using differen
t neural markers. Three phenotype markers characteristic of nerve cell
s, i.e., intense GABA, neuron-specific antigen (HPC-1) and microtubule
-associated protein 2 (MAP2) immunoreactivities, were detected in the
pineal culture of newborn rats. Expression of the respective neuronal
phenotypes appears to be controlled by different mechanisms; in the no
rmal culture medium containing 5.4 mM KCl, numerous cells were stained
intensely with anti-GABA antiserum, whereas only a few were stained i
ntensely either with HPC-1 or MAP2 antibody. In a culture medium with
a high concentration of KCl (35 mM), which may induce depolarization o
f nerve cells, numerous cells became strongly positive for HPC-1 or MA
P2; both the cell bodies and the neuritic fibers were stained positive
ly. Since cells intensely immunoreactive to GABA, HPC-I or MAP2 were n
ot found in intact pineals of the rat, the present results indicate th
at the neuronal potency of the rat pineal cells is expressed only in v
itro and is suppressed in vivo, and that the potency is lost during po
stnatal development. Norepinephrine at 1 mu M, which suppresses differ
entiation of rhodopsin immunoreactive cells, was ineffective in induci
ng phenotypic expression of neuronal properties in the present system,
indicating that the mechanism of suppression of neuronal properties i
n the intact pineal may be different from the one for photoreceptors.