We have previously demonstrated that
imidazole-4-acetic acid-ribotide (
IAA-RP) is present in the mammalian brain and is an endogenous
ligand at
imidazoline binding sites. In the present study, we used a polyclonal antiserum to visualize
IAA-RP-containing neurons in the rat caudoputamen. We observe
IAA-RP-immunostained neurons scattered throughout the dorsal and ventral striatum. Most of these cells co-localize
GABA, but none are
parvalbumin-immunoreactive. In contrast, approximately 50% of the
calbindin D28k-immunopositive striatal neurons co-localize
IAA-RP. Electrophysiological studies using corticostriatal slices demonstrated that bath application of
IAA-RP reversibly depresses the synaptically mediated component of field potentials recorded in the striatum by stimulation of cortical axons. Addition of competitive
glutamate receptor antagonists completely blocks the response, confirming its association with glutamatergic transmission. Using paired-pulse stimuli,
IAA-RP was shown to exert, at least in part, a presynaptic effect, but blockade of GABAA receptor-mediated transmission did not alter the response. Lastly, we show that this effect is attributable to imidazoline-1 receptors, and not to α2
adrenergic receptors. Since
IAA-RP is an endogenous central regulator of blood pressure, and cardiovascular dysfunction is a common symptom associated with
Parkinson's disease (PD), we speculate that
IAA-RP-related abnormalities may underlie some of the autonomic dysfunction that occurs in PD.