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Dopamine Receptors
Dopamine and dopamine receptors are most associated with their role in the brain, specifically the midbrain, i.e., the substantia nigra (SN). The SN is rich in dopaminergic neurons (also called dopamine neurons) that are the brain’s primary source of the neurotransmitter dopamine. Neurons from the SN project to the putamen via the nigrostriatal pathway. Cell death in this neuronal population is a hallmark of PD (Parkinson’s Disease) as this pathway is crucial for motor function.

There are five subclasses of dopaminergic neurons— D1, D2, D3, D4, and D5 — all of which are G-protein coupled receptors (GPCRs.) GPCRs are membrane bound receptors that, when activated, initiate downstream signaling that controls a myriad of potential effects within the cell, neighboring cells, or cells in other organs. The five subclasses are divided into two groups: D1 (D1-like) which includes D1 and D5, and D2 (D2-like) which includes D2, D3, and D4. D1 receptors are considered excitatory as they are G s bound, while D2 receptors are considered inhibitory as they are Gi/Go bound. The two classes are located post-synaptically and pre-synaptically, respectively. D2-like receptors often have roles as autoreceptors that modulate the function of a cell via a negative feedback loop. For example, dopaminergic neurons secrete dopamine that binds to D2 receptors on the same cell which then inhibit further dopamine release. This allows the neuron firing rate to be fine-tuned by neurotransmitters outside of the cell.

Dopamine Receptors in the Pancreas
Dopamine receptors are not limited to the brain: they are expressed in many organs outside of the brain, also called the periphery. Expression of dopamine receptors has been found in the eyes, heart, gastrointestinal tract, kidney, and other organs. The pancreas is one of these organs that D2 receptors play a crucial role in.

The role of the pancreas is to secrete digestive enzymes via exocrine glands and hormones via endocrine glands. Pancreatic endocrine glands, comprised of dense clusters of cells called the islets of Langerhans, secrete insulin, glucagon, and other hormones essential for metabolism and glycemic control. Insulin secreting beta cells have been intensely researched due to their role in diabetes.

Recent studies have found that beta cells, as well as other endocrine and exocrine pancreatic cells, express D2 receptors and that beta cells co-secrete dopamine along with insulin. Dopamine has been purported to be a negative regulator of insulin, meaning that bound D2 receptors inhibit insulin secretion. This connection between dopamine and beta cells was partially discovered due to the metabolic side-effects of certain antipsychotic medications. Traditional/typical antipsychotic medications function by altering the dopamine pathway in the brain, such as blocking D2 receptors. Common side effects of these medications are rapid weight gain and glycemic dysregulation among others. The effects of these medications are not limited to the brain, so off-target effects in other organs such as the pancreas have been proposed as a possible mechanism.