Background:Various effects of steroid hormone activity cannot easily be explained by the action of classical nuclear receptors and genomic signal transduction pathways. These activities are manifested principally as rapid processes, lasting from seconds to minutes, resulting in changes in ion transduction, calcium intracellular concentration, and level of the second messengers, which cannot be realized through the genomic pathway. Hence, it has been proposed that other kinds of mediators should be involved in steroid-induced processes, namely receptors located on the cell surface. The search for their chemical nature and role is of utmost importance. Current state of knowledge confirms their relation to GPCRs. Moreover, it seems that almost every nuclear receptor specific for steroid hormone family has its membrane-bound equivalent.
Objective:In this review, we summarize current state of knowledge about nuclear and membrane receptors for progesterone, and describe their potential functions alone, as well as in cooperation with other receptors.
Conclusion:In the light of common expression, both in species and organs, membrane receptors could play a role that is at least comparable to nuclear receptors. Further exploration of membrane receptor-dependent signaling pathways could give a new insight in the treatment of many endocrine and oncological pathologies.
OBJECTIVES
Perivascular adipose tissue (PVAT) surrounding the human internal thoracic artery exhibits anticontractile and vasorelaxing properties associated with the adipocyte-derived relaxing factor (ADRF). The goal of our study was to assess if perivascular tissue of the human radial artery (RA) also exhibits such anticontractile/vasorelaxant properties. It could be especially relevant in preventing RA spasms.
METHODS
The study was performed on isolated segments of human pedicled RA. Its skeletonized fragments were suspended on stainless steel wire hooks and gradually contracted with serotonin to establish the concentration–effect relationship in the presence/absence of PVAT. Skeletonized arterial segments were precontracted with a single dose of 10−6 M serotonin (EC80). The 5-ml PVAT aliquots (from PVAT incubated in Krebs–Henseleit solution) were transferred to the RA tissue bath resulting in its relaxation. Subsequently, we investigated if ADRF is dependent on endothelial vasorelaxants (nitric oxide and prostacyclin). We attempted to find the potassium channel responsible for mediating the activity of ADRF using different potassium channel blockers.
RESULTS
RA without PVAT contracted more strongly in response to serotonin compared to RA with PVAT [Emax: 108.3 (20.2) vs 76.1 (13.5) mN]. The PVAT aliquot relaxed precontracted RA rings at 43% (2.4%) [72.2 (15.6) to 41.0 (5.6) mN]. ADRF is independent of endothelial vasorelaxants; hence, the addition of NG-monomethyl-L-arginine and indomethacin did not change the vasorelaxant response. Neither of the potassium channel blockers participated in the activity of ADRF.
CONCLUSIONS
PVAT of human RA exhibits anticontractile/vasorelaxant properties that are inherently associated with ADRF secretion. We confirmed the endothelial-independent mechanism of the activity of ADRF. However, we failed to find the potassium channel responsible for the action of ADRF.
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