Abstract

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.

Links

Publisher Full Text

Authors

Martir JF, Bozdagi O, Martinelli GP, Friedrich VL, Holstein GR

Institution

Department of Neurology, Functional Morphology Mount Sinai School of Medicine, New York, NY 10029, USA.

Source

Acta biologica Hungarica 63 Suppl 1: 2012 pg 5-18

MeSH

Animals
Autonomic Nervous System
Basal Ganglia
Calcium-Binding Protein, Vitamin D-Dependent
Electric Stimulation
Evoked Potentials
Excitatory Amino Acid Antagonists
GABA-A Receptor Antagonists
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
Synaptic Transmission
Time Factors
gamma-Aminobutyric Acid

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22453739