Dale's principle

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Dale's Principle (or Dale's Law) was ascribed to the English neuroscientist Henry Hallett Dale. As commonly posited, Dale's Principle states that, although different neurotransmitters can be produced at different synapses within the brain, an individual neuron is capable of releasing only one and only one neurotransmitter from its axonal terminals. In fact, Dale never made such an absolute declaration. Most importantly, Dale's Principle is probably false. Recent studies in a myriad of systems have shown that most, if not all, neurons release several different chemical messengers. One of the early elegant examples of cotransmission explained an old anomaly of atropine resistant vasodilation in parasympathetic salivary gland function. It was shown that these neurons released acetylcholine (primarily responsible for secretion) and the neuropeptide VIP (primarily responsible for vasodilation). Only the former can be blocked by the cholinergic antagonist atropine. In modern neuroscience, neurons are often classified by their cotransmitter, for example striatal GABA neurons utilizing opioid peptides or substance P as the primary cotransmitter.

Examples of neuron types releasing two or more neurotransmitters at the same time and include:

• GABA-gylcine co-release.
• Acetylcholine-glutamate co-release.
• Dopamine-glutamate co-release.
• Acetylcholine (ACh) and vasoactive intestinal peptide (VIP) co-release.
• Acetylcholine (ACh) and calcitonin gene-related peptide (CGRP) co-release.
• Glutamate and dynorphin co-release (in the hippocampal synapses).

Dale stated that a neurotransmitter must:

• be synthesized in nerve terminals;
• be stored in synaptic vesicles;
• be released in response to neuronal stimulations;
• act on a postsynaptic receptor; and
• undergo transmitter reuptake

-- Dale probably never actually stated that a neuron could not release two substances -- it was not a theoretical concern at the time.