Mast cells (MCs) were first described by Paul Ehrlich as well fed granular cells that stain metachromatically. Today MCs are regarded as multifunctional, granulated, tissue-dwelling cells distributed in the perivascular spaces and connective tissues of every major organ of the body. Their long recognized phenotypic diversity might be associated not only with their anatomic distribution and mediator repertoire, but also with their functional characteristics related to the regulation of effector pathways. In addition to their historical involvement in type I hypersensitivity response, MCs have emerged as versatile effector cells with functional diversity and homeostatic functions in non-IgE-mediated inflammatory responses, autoimmunity, bidirectional interactions with the neuroendocrine circuit, the urinary, gastrointestinal, cardiovascular and endocrine systems, in metabolism and malignancy. Thus, MCs appear to receive, integrate and transmit a wide range of signals in their microenvironment, coordinated by the differential release of their pro-inflammatory and anti-inflammatory granular mediators. Understanding the heterogeneity of this complex cellular communication may provide a tool for selective pharmacological intervention directed to specific MC subsets.

The cellular stress response is a universal protective reaction to adverse environmental or microenvironmental conditions, such as heat and drugs, associated in part with the highly conserved heat shock proteins (HSPs). Histamine is a key inflammatory mediator derived from L: -histidine that governs vital cellular processes beyond inflammation, while recent evidence implies additional actions in both prokaryotes and eukaryotes. This study explored the possible role of histamine in the heat shock response in yeast, an established experimental model for the pharmacological investigation of the cellular stress response. The response was evaluated by determining growth and viability of post-logarithmic phase grown yeast cultures after heat shock at 53 degrees C for 30 min. Thermal preconditioning at 37 degrees C for 2 h served as a positive control. The effect of histamine was investigated following long-term administration through the post-logarithmic phase of growth or short-term administration for 2 h prior to heat shock. Short-term treatment with 1 mM histamine resulted in de novo protein synthesis-dependent acquisition of thermotolerance, while lower doses or long-term administration of histamine failed to induce the heat-resistant phenotype. Preliminary investigation of HSP104, HSP70 and HSP60 expression by western blotting showed an increase of these proteins after thermal preconditioning. However, a differential HSP and tubulin expression appeared to underlie the response of yeast cells to histamine. In conclusion, histamine was capable of inducing the adaptive phenotype, while the contribution of HSPs and tubulin and the potential implications remain largely elusive.

Aims: Histamine interacts with the stress response in eukaryotes. This study investigated the effects of antihistamines on the heat shock (HS) response in yeast, thereby exploring their functions in a well-established histamine receptor (H x R)-free model. Methods and Results: Stress response was evaluated by determining growth and viability of postlogarithmic phase grown yeast cultures after HS at 53°C for 30 min. The effects of H x R ligands were investigated following short-and long-term administration. The H 1 R antagonist dimethindene exerted doserelated antifungal actions, whereas the H 2 R antagonist ranitidine failed to elicit any effect. In contrast, the H 3/4 R and H 4 R ligands, thioperamide and JNJ7777120, respectively, induced the thermotolerant phenotype. The circumvention of thermotolerance by cycloheximide and the induction of Hsp70 and Hsp104 expression indicated the contribution of de novo protein synthesis in the adaptive process, likely directed towards alterations in Hsp expression. Conclusions: The data provide evidence for the differential function of H x R ligands in thermotolerance induction in yeast. Significance and Impact of the Study: First demonstration of the action of antihistamines in the HS response in yeast. The work supports the potential H x R-independent functions of histaminergic compounds in fungal adaptation and stimulates research on the prospect of their exploitation in eukaryotic (patho)physiology.

The cellular stress response (CSR) is a universal inducible reaction modulated, among others, by heat, drugs, and hormones. We aimed to investigate the role of L-thyroxine (T4) on the heat shock (HS) response in Saccharomyces cerevisiae. The CSR was evaluated by determining growth and viability of post-logarithmic phase grown yeast cultures after HS at 53°C for 30 min. We found that long-term T4 exposure can induce a dose-dependent and Hsp90 and H + trafficking-related thermotolerance in yeast.