How does the fact that different dopamine receptors have different shapes affect reactions that happen in cells due to the binding of the dopamine molecule? I was under the impression that the binding of the molecule was the first stage and the subsequent reactions would then be the same, but if having different dopamine receptors changes a person's behaviour then this cannot be correct.
Thanks!

There are different types of dopamine receptors and they have different functions:
https://en.wikipedia.org/wiki/Dopamine_receptor

agreed and to add - the "shape" which is determined by the amino acid structure is important but the down-stream intracellular signalling pathways that the different receptors link to is just, if not more, important for their differing functions.

Dopamine receptors are members of the G protein-coupled receptor (GPCR) superfamily. GPCRs have a dynamic structure that can assume a spectrum of conformational states. Upon ligand binding there are changes in the GPCR that lead to structural re-arrangements that facilitate interaction with intracellular effectors (as David points out) such as G proteins, kinases and arrestins that leads to the activation of a plethora of signalling molecules and cascades. These structural changes have been determined by biochemical, biophysical and mutagenesis studies and validated more recently by X-ray crystallography of a number of GPCRs.

Dopamine receptors comprise 5 structurally-related members and fall into 2 classes; the D1-like (D1 and D5) and D2-like (D2, D3 and D4). The genes for the former are intronless while the D2-like receptor genes have introns (interrupting their protein-coding sequences) so they can have alternatively-spliced forms that can confer different pharmacological properties. Subleties in the orientation of the 7 transmembrane helices of each dopamine receptor as well as differences in intracellular and extracellular domains confer the pharmacological and biochemical properties that make each dopamine receptor unique. Broadly speaking D1-like receptors tend to bind Gs protein to activate adenyl cyclase (raising cyclic AMP) whereas D2-like receptors bind to Gi/o proteins to inhibit adenyl cyclase, but the D2's can also bind to other G proteins such as Gq (which often leads to intracellular calcium mobilization).

Where dopamine receptors 'live' is obviously integral to their function. They may reside on different tissues or brain regions, on separate cells, or be located pre- or post-synaptically. Some dopamine receptors may be co-expressed in the same neuron and may interact at the physical level (e.g., by receptor dimerization) or cross-talk via converging intracellular pathways. e.g., D1 and D2 receptors have opposing effects on intracellular sodium in striatal neurons in the basal ganglia (http://www.ncbi.nlm.nih.gov/pubmed/10700253). So the final functional output of a cell may be the result of the coordinate activation of dopamine receptors (expressed on the same or different cells) and in collaboration with many other receptors and intracellular signalling pathways (bare in mind that the average neuron expresses hundreds of receptors!).

There are many good references on dopamine receptors (e.g., see - http://pharmrev.aspetjournals.org/conte … 182.full). There is also a good general database on all GPCRs (http://www.guidetopharmacology.org/) that summarizes details on the 5 dopamine receptors.

Last edited by Steve Lolait (21st Mar 2016 11:58:20)