imidazoleacetic-acid-ribotide and Parkinson-Disease

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.

Topics: Animals; Autonomic Nervous System; Basal Ganglia; Calbindin 1; Calbindins; Electric Stimulation; Evoked Potentials; Excitatory Amino Acid Antagonists; GABA-A Receptor Antagonists; gamma-Aminobutyric Acid; Imidazoles; Imidazoline Receptors; Ligands; Male; Microscopy, Fluorescence; Motor Activity; Neural Inhibition; Neurons; Parkinson Disease; Rats; Rats, Long-Evans; Rats, Sprague-Dawley; Receptors, GABA-A; Ribosemonophosphates; S100 Calcium Binding Protein G; Synaptic Transmission; Time Factors