noncholinergic

Noncholinergic refers to signaling, innervation, or actions that do not involve acetylcholine as the transmitter or cholinergic receptors. In physiology and pharmacology, the term is often used to describe components of the autonomic nervous system that operate independently of cholinergic transmission, and is commonly paired with nonadrenergic (NANC) to denote fibers that release transmitters other than norepinephrine and acetylcholine.

Noncholinergic signaling encompasses a variety of transmitter systems. The most studied are nitric oxide (NO)–mediated nitrergic pathways, and peptide or purinergic transmitters such as vasoactive intestinal peptide (VIP), neuropeptide Y, substance P, and adenosine triphosphate (ATP). NO often serves as an inhibitory transmitter, causing smooth muscle relaxation in tissues like the gastrointestinal tract, genitourinary tract, and airways. ATP can act as an excitatory or modulatory co-transmitter in different contexts, while VIP and other neuropeptides contribute to modulation of motility, secretion, and blood flow.

In practical terms, noncholinergic mechanisms become evident when cholinergic transmission is blocked or absent, revealing residual or alternative pathways that regulate activity such as smooth muscle tone and glandular secretion. The concept is especially relevant in the gut and urinary tract, where nitrergic and other noncholinergic nerves coordinate motility and relaxation. Dysfunction of noncholinergic signaling has been implicated in various disorders, including esophageal or gastric motility disturbances and certain forms of urinary dysfunction.

Overall, noncholinergic describes a broad set of signaling mechanisms that operate independently of acetylcholine, contributing to the regulation of smooth muscle function and organ physiology.