Receptors Involved in the Vomiting Reflex
The principal neuroreceptors involved in the emetic response are serotonin (5-HT3) and dopamine receptors, with additional contributions from neurokinin-1 (NK-1), acetylcholine, corticosteroid, histamine, cannabinoid, and opiate receptors. 1
Primary Receptor Systems
Serotonin (5-HT3) Receptors
- 5-HT3 receptors are located both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema, making them critical targets for antiemetic therapy 2
- These receptors mediate rapid excitatory responses when serotonin is released from enterochromaffin cells in the small intestine following exposure to chemotherapeutic agents or other emetogenic stimuli 3, 4
- The vagal afferents are stimulated through 5-HT3 receptors, initiating the vomiting reflex 2
Dopamine Receptors
- Dopamine receptors, particularly D2 receptors, are principal neuroreceptors in the emetic response and are located in the chemoreceptor trigger zone 1
- Dopamine receptor agonists can directly trigger emesis, while antagonists (such as metoclopramide and haloperidol) provide antiemetic effects 1, 5
Secondary Receptor Systems
Neurokinin-1 (NK-1) Receptors
- NK-1 receptors respond to substance P and are located in the vomiting and vestibular centers of the brain 1
- These receptors play a particularly important role in delayed emesis and can be effectively blocked by aprepitant or fosaprepitant 1
Other Contributing Receptors
- Acetylcholine, corticosteroid, histamine, cannabinoid, and opiate receptors are all located in the vomiting and vestibular centers and contribute to the emetic response 1
- Histamine H1 receptors and muscarinic M1 receptors can trigger intracellular calcium signaling that leads to emesis 6
Anatomical Organization
The Vomiting Center
- The vomiting center in the medulla receives afferent impulses from four primary sources: the chemoreceptor trigger zone, pharynx and gastrointestinal tract (via vagal afferent fibers), and cerebral cortex 1, 7
- Efferent impulses from the vomiting center are transmitted to the salivation center, abdominal muscles, respiratory center, and cranial nerves to produce the coordinated vomiting response 7
The Chemoreceptor Trigger Zone
- The chemoreceptor trigger zone in the area postrema detects circulating toxins, drugs, and metabolites in the blood 7
- This zone contains high concentrations of neurotransmitter receptors, particularly 5-HT3 and dopamine receptors 1
Clinical Implications
Receptor-Targeted Antiemetic Therapy
- No single antiemetic agent can provide complete protection because no final common pathway for emesis has been identified, necessitating multi-receptor targeting 1
- Each antiemetic agent predominantly blocks one receptor type at therapeutic concentrations, explaining why combination therapy is more effective than monotherapy 1
- Antiemetic agents can block different neuronal pathways and exert effects at different points during the emetic response, behaving synergistically when combined 1
Calcium Signaling as a Common Pathway
- Activation of diverse emetic receptors (NK1, 5-HT3, D2, M1, or H1) triggers calcium-dependent release of neurotransmitters from enterochromaffin cells and brainstem neurons 6
- L-type calcium channel blockers demonstrate broad-spectrum antiemetic efficacy by interrupting this common signaling pathway 6