Muscarinic and histamine receptor signaling

Muscarinic and histamine receptor signaling encompasses the complex intracellular pathways activated by two distinct families of G protein-coupled receptors (GPCRs): muscarinic acetylcholine receptors (mAChRs) and histamine receptors (HRs) (IUPHAR/BPS Guide to Pharmacology). Muscarinic receptors, categorized into five subtypes (M1-M5), are essential for parasympathetic nervous system function, regulating heart rate, glandular secretion, and smooth muscle contraction, as well as cognitive functions in the brain (UniProt). Histamine receptors, comprising four subtypes (H1-H4), play pivotal roles in the inflammatory response, gastric acid production, and the regulation of the sleep-wake cycle (StatPearls). Many therapeutic agents, such as first-generation antihistamines (e.g., diphenhydramine) and tricyclic antidepressants, act as non-selective antagonists across both receptor systems (PubMed). While this dual activity is beneficial for treating multi-factorial conditions like motion sickness or severe emesis, it frequently leads to significant side effects, collectively known as "anticholinergic" and sedative effects, which can limit clinical utility, especially in geriatric populations (NIH).

Other names

Muscarinic-histaminergic signalingmAChR and HR signaling pathwayCholinergic and histaminergic crosstalkMuscarinic and histamine receptor pathways

Competitive antagonism of muscarinic acetylcholine receptors (M1-M5) and histamine receptors (primarily H1 and H2), leading to the inhibition of downstream G protein-mediated signaling cascades such as the phospholipase C (PLC) or adenylyl cyclase pathways (IUPHAR/BPS Guide to Pharmacology).