Molecular thermosensation in the peripheral nervous system

Platelets play an important role in the coronary thrombus formation that leads to myocardial ischemia. Receptors for the steroid hormone estrogen are present on platelets, and may mediate gender-specific trends in cardiovascular disease by affecting thrombogenicity. We characterize human platelet ER β and its expression using biochemical and molecular biologic techniques. Investigation of platelet ER β mRNA by RT-PCR revealed normal transcripts with tissue-specific glycosylation, and a single alternately spliced mRNA that is unlikely to produce a functional protein. These platelet specific forms of ER β are unlikely to mediate gender-specific platelet function, but may have dominant negative effects in the signaling cascade.; Expression of TRPV1 within the bladder has been observed in afferent neurons innervating the muscular wall; we propose that epithelial cells may also signal via this receptor. NO is believed to modulate bladder reflexes by altering afferent nerve activity, so we examined the urothelial cells for isoforms of NOS. We looked for expression of TRPV1 in bladder smooth muscle and urothelium, and evaluated mice lacking TRPV1. Sensitivity of bladder structures to cooling compounds also led us to assess the expression of the cold-activated channels TRPM8 and ANKTM1. Bladder urothelial cells express TRPV1, epithelial NOS, and inducible NOS; lack of TRPV1 appears to disrupt normal bladder physiology. Urothelial cells also express TRPM8 and ANKTM1; their expression levels are modulated by pathological bladder conditions.; Several candidate cold receptors have been proposed to be involved in peripheral thermosensation. One of these, TRPM8, is activated both by decreases in temperature and the cooling agents menthol and icilin. Here, we use fluorometric calcium imaging of cultured trigeminal neurons to demonstrate that there are distinct subpopulations of cold responsive neurons; single-cell RT-PCR analysis suggests that TRPM8 likely contributes to cold transduction in one of them. We also investigate the suggestion that TRPM8 and ANKTM1 (which is also activated by cold temperatures) have different sensitivities to icilin. Calcium imaging experiments using both cold stimulation and subsequent icilin exposure confirm that cells with a TRPM8 phenotype tend to be more sensitive to icilin than cells that have a cold response profile like ANKTM1.