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Histamine induces peripheral and central hypersensitivity to bladder distension via the histamine H1 receptor and TRPV1

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Occupancy stays low, but each engaged receptor keeps sending its main message longer than it would under a balanced signal (cAMP bias with low receptor internalization). In a head-to-head trial against liraglutide, tirzepatide reduced measured food intake and craving more despite lower GLP-1 occupancy. The effect lowers the drive to eat rather than increasing restraint