Table 1. Catechol-O-methyltransferase endogenous catechol substrates, their receptors and function.

Endogenous substrates	Receptor	Biological function
Dopamine	Dopamine family of receptors (DRD1–5)	Neurotransmission of reward and incentive salience, motor control. Dopamine inhibits norepinephrine release, acts as a vasodilator, and can increase sodium excretion and urine output. In the pancreas, dopamine reduces insulin production and reduces gastrointestinal motility in the digestive system; in the immune system, it reduces the activity of lymphocytes. Dopamine is converted to norepinephrine by DBH
Norepinephrine	α and β-adrenergic receptors (ADRα and β)	Norepinephrine is a key neurotransmitter in the sympathetic nervous system and is important in the fight-or-flight response. It acts by increasing heart rate, blood pressure and glucose levels, while also increasing blood availability in skeletal muscle and reducing it in the GI tract. Norepinephrine is converted to epinephrine by PNMT
Epinephrine	α and β-adrenergic receptors (ADRα and β)	Like norepinephrine, epinephrine is important in the fight-or-flight response, increasing heart and respiratory rate, muscle contraction, vasomotor tone, blood glucose and lipolysis. Epinephrine is derived from norepinephrine by PNMT
Catechol estrogen	Membrane (mER) and nuclear estrogen receptors (ERα and ERβ)	Estrogen is converted to catechol estrogens by cytochrome P450 enzymes. Catechol estrogens have procarcinogenic, proproliferative, and anti-apoptotic activities. COMT converts catechol estrogens to methoxyestradiols that are protective against carcinogenesis

COMT: Catechol-O-methyltransferase; DBH: dopamine β-hydroxylase; GI: Gastro-intestinal; PNMT: Phenylethanolamine N-methyltransferase