Insights into the physiomodulatory role of histaminergic receptors in vertebrate skin pigmentation.

All organisms, from simple invertebrates to complex human beings, exist in different colors and patterns, which arise from unique distribution of pigments throughout the body. Being the largest organ of the body, skin is always under the influence of internal and external factors that often react to certain intrinsic agents in an unorthodox manner, modifying the integral pigmentation patterns and resulting into complex physiological aberrancies. One of these intrinsic agents involved in numerous immunological and non-immunological processes within the body is histamine. Histamine mediates its multifarious biological activities stimulated by various immunological and non-immunological stimuli via differential expression of its four classes of receptors (H1, H2, H3, and H4) on effector cells. Interestingly, recent studies have described the expression of functional histamine receptors in vertebrate pigment cells melanocytes, emphasizing the potential physiomodulatory effects of this molecule in the phenomenon of skin pigmentation. This noteworthy finding has opened numerous perspectives to elucidate several contentions regarding skin-related conditions. The focus of this review is to provide an updated overview of the involvement and role of histamine and its receptors together with the physiological and pharmacological aspects of their agonists and antagonists impinging the phenomenon of pigmentation and the mechanisms by which they do so.