Related Experiment Video
Updated: Aug 23, 2026

HSV-Mediated Transgene Expression of Chimeric Constructs to Study Behavioral Function of GPCR Heteromers in Mice
Published on: July 9, 2016
Histamine H1 receptor down-regulation mediated by M3 muscarinic acetylcholine receptor subtype
Katsuhiro Miyoshi1, Nozomi Kawakami, Yousuke Wakayama
1Department of Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770-8505, Japan.
Abstract:
Heterologous down-regulation of histamine H(1) receptor (H1R) mediated by muscarinic acetylcholine receptor subtype was investigated using five kinds of Chinese hamster ovary (CHO) cells stably co-expressing the human H1R and one of the five (M(1) - M(5)) muscarinic acetylcholine receptors, CHO-H1/M1, CHO-H1/M2, CHO-H1/M3, CHO-H1/M4, and CHO-H1/M5 cells. Among the CHO-H1/M1, CHO-H1/M3, and CHO-H1/M5 cells, carbachol treatment of the CHO-H1/M3 cells time-dependently led to remarkable down-regulation of the H1R to 60% of the control level. In contrast, stimulation of CHO-H1/M1 cells by carbachol induced negligible effect on the down-regulation. Stimulation of CHO-H1/M5 cells by carbachol induced significant but only small H1R down-regulation. M(2) and M(4) muscarinic receptors showed negligible effect on the down-regulation. H1R-mediated accumulation of inositol phosphates in CHO-H1/M3 cells with long-term expose to carbachol was decreased to 60% compared with non-treated cells. Heterologous phosphorylation of H1R was induced by the stimulation of each muscarinic receptor. H1R was phosphorylated by about twofold from the basal level through five subtypes of muscarinic receptor. The M(3) muscarinic receptor-mediated phosphorylation of H1R was reversed by the inhibition of protein kinase C. In the present study we demonstrated that the M(3) muscarinic acetylcholine receptor mediated remarkable down-regulation of the H1R with decreased receptor signaling.
Related Concept Videos
Cholinergic Receptors: Muscarinic
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...
Cholinergic Antagonists: Pharmacological Actions
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...
Antiasthma Drugs: Muscarinic Receptor Antagonists
Antimuscarinic agents compete with ACh for the same binding site on the muscarinic receptors. By binding to these receptors, they inhibit the downstream effects of ACh and block the parasympathetic...
Direct-Acting Cholinergic Agonists: Pharmacological Actions
Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists
Parasympathetic Signaling
The effects of...

