Neurotransmission, brain receptor site

A principal interest in our laboratory is the molecular characterization of CNS receptor sites of the neurotransmitter dopamine (DA, 5). These sites are strongly implicated in the biochemical etiology of schizophrenia and Parkinson s Disease, as well as other diseases of the CNS (50,51). Thus, the rank order of clinical potency of antipsychotic drugs (neuroleptics) correlates with the affinity of these drugs for dopaminergic sites (52,53), It is also well established that Parkinson s disease is directly related to deterioration in dopaminergic neurotransmission in the corpus striatum, which is a brain region rich in dopamine receptor sites (54). The use of L-DOPA, the biosynthetic precursor of dopamine, in treatment of patients with Parkinson s disease is one of the best examples of biochemically directed medical treatment. 

All the pharmacological and behavioural effects elicited by dopamine agonists and antagonists in the brain can only be explained if such an interaction occurs at the level of the dopamine receptor (D2 receptor site) the site still remains in search of a function. Bovine parathyroid cells were reported to possess dopamine sites which should be involved in the control of parathormone secretion. However, the very poor pharmacological characterization and the lack of in vivo evidence do not allow to assess the dopaminergic nature of this hormone secretion. Dopamine-sensitive adenylate cyclase is thus not a receptor directly implicated in the dopaminergic neurotransmission it is an enzyme which could have an important role in the control of long term metabolic effects such as the synthesis of neuronal constituents. 

FIGURE 5—70. Substance P and neurokinin 1 receptors, part 3. Shown here is how substance P is formed from gamma PPT-A. Thus, substance P can be formed from three proteins derived from the PPT-A gene, namely, alpha, beta, and gamma PPT-A (see also Figs. 5-68 and 5-69). When substance P is released from neurons, it prefers to interact selectively with the neurokinin 1 subtype of neurokinin receptor (Figs. 5-68 to 5-70). However, there is a mismatch in the brain between the locations of substance P and the NK-1 receptors, suggesting that substance P acts preferentially by volume neurotransmission at sites remote from its axon terminals rather than by classical synaptic neurotransmission. 

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