Aminopeptidase Activity in the Nigrostriatal System and Prefrontal Cortex of Rats with Experimental Hemiparkinsonism

Introduction

Parkinsonian patients and animals with experimental parkinsonism exhibit not only alterations in motor behavior but also autonomic and neuroendocrine dysfunction [1]. In the striatum, neuropeptides such as cholecystokinin (CCK) [2], angiotensin [3] and enkephalin [4] coexist together with dopamine (DA). Their role in the striatal function and pathophysiology of neurodegenerative diseases that frequently affect the nigrostriatal system is not yet understood. In addition, a large number of CCK-containing striatal fibers have been reported to originate from medial prefrontal cortical areas [5] that also modulate neuroendocrine and autonomic functions [6]. Due to their possible involvement in some brain disorders such as Parkinson’s disease or schizophrenia, there is great interest in the functional role of DA and neuropeptides that coexist with this catecholamine in striatum and basal forebrain [7].

Neuropeptides released into the synaptic cleft are assumed to be hydrolyzed after activation of membrane receptors, predominantly by membrane-bound peptidases, and are thus inactivated or biotransformed. Aminopeptidases (APs), the most abundant proteolytic enzymes in the brain, play a major role in controlling neuropeptide function. Therefore, while interaction between DA and several neuropeptides has been studied to some degree, the relationship between DA and AP activity in the nigrostriatal system and basal forebrain has received little attention. In the present work, the effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal system on AP activity was investigated in adult male rats. After intrastriatal injection of 6-OHDA or saline unilaterally in the left striatum, membrane-bound alanyl- (AlaAP), cystinyl- (CysAP), aspartyl- (AspAP) and glutamyl-aminopeptidase (GluAP) activity was determined in left striatum, left substantia nigra and left prefrontal cortex using arylamides as substrates. These enzymes’ involvement has been demonstrated in the metabolism of CCK (GluAP, AspAP) [8], angiotensins (GluAP, AspAP, AlaAP, CysAP) [9] and enkephalins (AlaAP) [10].

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