Social Stress Upregulates Histamine H3 Receptor mRNA in Murine Urinary Bladder Smooth Muscle

Abstract

In mice, social stress causes mast cell degranulation and alters voiding behavior. Histamine, a mast cell‐derived biogenic amine, is hallmarked as a modulator that can drive neurogenic bladder overactivity. Additionally, histamine causes a rapidly desensitizing contraction of the urinary bladder smooth muscle (UBSM) in normal mice that is H1 receptor‐dependent. However, histamine receptor expression in UBSM after social stress is unclear. We sought to determine if the expression of histamine receptors change in urinary bladder smooth muscle cells after social stress. We hypothesized that histamine H1 receptor expression would be upregulated in UBSM cells collected from stressed mice as compared to non‐stressed. Prior to cell isolation and collection, 4‐week‐old C57BL/6 male mice were randomly housed with CD1 adult male aggressor mice for 5 minutes, after which both mice were placed in barrier housing for 1 hour. Social stress was repeated with different aggressor mice for 14 days. Afterward, bladders were enzymatically dissociated, and urinary bladder smooth muscle cells were isolated for single cell qRT‐PCR. Non‐stressed UBSM cells expressed only Hrh1and Hrh2 mRNA. However, UBSM cells from stressed mice also expressed Hrh3 mRNA. These data suggest that social stress alters histamine receptor expression in UBSM, specifically by upregulating histamine H3 receptor expression. Since H3 receptors are involved in inflammatory peptide release in other organ systems, the functional role of H3 receptors in stress‐induced bladder dysfunction warrants further investigation.