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issue 3
515-522
EN
Kinins, universal mediators of inflammation, are recognized by two kinds of receptors, B1 and B2, which have been found to be expressed in numerous cell types of several species. However, the knowledge of the regulation of these receptors in leukocytes is still not satisfactory. In the current work, we have demonstrated a constitutive production of B2 receptor mRNA in the human promonocyte U937 cells and its two-fold augmentation after cell differentiation with retinoic acid and phorbol ester. Bradykinin and des-Arg10-kallidin induced the expression of both B2 and B1 receptors in cells before and after differentiation. Generally, the undifferentiated cells were more susceptible to bradykinin-dependent induction of kinin receptors (increases by approximately 250% and 200% for B2 and B1 receptors, respectively). The induction, by approx. 200%, of B1 receptor by des-Arg10-kallidin was detected on both mRNA and protein levels. In addition, an unexpected strong induction of B2 receptor by this compound was observed in the retinoic acid- and phorbol ester-differentiated cells (by 150% and 200%, respectively) that suggests a possible autoregulation of kinin receptors by own agonists during the inflammatory state. On the other hand, a strong enhancement of the expression of both receptors by interleukin 1β, especially in the phorbol ester-differentiated cells, indicates the involvement of kinin receptors in the propagation of the inflammatory processes.
EN
The G protein-coupled receptors (GPCRs), one of the largest protein families, are essential components of the most commonly used signal-transduction systems in cells. These receptors, often using common pathways, may cooperate in the regulation of signal transmission to the cell nucleus. Recent scientific interests increasingly focus on the cooperation between these receptors, particularly in a context of their oligomerization, e.g. the formation of dimers that are able to change characteristic signaling of each receptor. Numerous studies on kinin and dopamine receptors which belong to this family of receptors have shown new facts demonstrating their direct interactions with other GPCRs. In this review, current knowledge on signaling pathways and oligomerization of these receptors has been summarized. Owing to the fact that kinin and dopamine receptors are widely expressed in cell membranes where they act as mediators of numerous common physiological processes, the information presented here sheds new light on a putative crosstalk of these receptors and provides more comprehensive understanding of possible direct interactions that may change their functions. The determination of such interactions may be useful for the development of new targeted therapeutic strategies against many disorders in which kinin and dopamine receptors are involved.
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