Muscarinic receptors 2 and 5 regulate bitter response of urethral brush cells via negative feedback.

We have recently identified a cholinergic chemosensory cell in the urethral epithelium, urethral brush cell (UBC), that, upon stimulation with bitter or bacterial substances, initiates a reflex detrusor activation. Here, we elucidated cholinergic mechanisms that modulate UBC responsiveness. We analyzed muscarinic acetylcholine receptor (M1-5 mAChR) expression by using RT-PCR in UBCs, recorded [Ca2+]i responses to a bitter stimulus in isolated UBCs of wild-type and mAChR-deficient mice, and performed cystometry in all involved strains. The bitter response of UBCs was enhanced by global cholinergic and selective M2 inhibition, diminished by positive allosteric modulation of M5, and unaffected by M1, M3, and M4 mAChR inhibitors. This effect was not observed in M2 and M5 mAChR-deficient mice. In cystometry, M5 mAChR-deficient mice demonstrated signs of detrusor overactivity. In conclusion, M2 and M5 mAChRs attenuate the bitter response of UBC via a cholinergic negative autocrine feedback mechanism. Cystometry suggests that dysfunction, particularly of the M5 receptor, may lead to such symptoms as bladder overactivity.-Deckmann, K., Rafiq, A., Erdmann, C., Illig, C., Durschnabel, M., Wess, J., Weidner, W., Bschleipfer, T., Kummer, W. Muscarinic receptors 2 and 5 regulate bitter response of urethral brush cells via negative feedback.

[Osteological case study to narrow the timing of postmortem trauma to a skull]. / Steologische Fallstudie zur zeitlichen Eingrenzung einer postmortalen Schädelverletzung.

In the course of an exhumation performed 5.5 years after death, several bone fragments were uncovered during the excavation of the clay-rich soil. Amongst others, there was a large piece of the frontal neurocranium. In addition, a so-called coffin stain was discernible. The exhumed coffin was intact. The forensic autopsy revealed a complete corpse with distinct adipocere formation. Consultation with the cemetery administration allowed the conclusion that the additional bone fragments were from the first use of the grave approximately 100 years ago. The heavily soil-encrusted skull fragment bore clear signs of a half sharp force, that could immediately be classified as postmortem. The pattern of injury pointed to an excavator as the cause. However, the question arose whether the postmortem trauma occurred 5.5 years ago during the excavation of the grave or during the current exhumation. First the skull fragment was dried. However, it was then impossible to remove the clay-rich soil without damaging the bone. The fragment was therefore carefully washed and dried again. The cut and fracture areas then showed distinctly lighter surfaces than the rest of the bone, which pointed to the exhumation as the time of origin. For comparison, fresh injuries were inflicted with a hatchet. These distinctly showed even lighter surfaces, so that the time of origin could be assumed to have been during the excavation of the grave 5.5 years ago.