Defining the roles of arrestin2 and arrestin3 in vasoconstrictor receptor desensitization in hypertension.
Bottom Line: Desensitization of UTP-stimulated vessel contractions was increased in 12-wk-old (but not 6-wk-old) SHR animals.In conclusion, arrestin2 and 3 expression is elevated in resistance arteries during the emergence of the early hypertensive phenotype, which underlies an enhanced ability to desensitize vasoconstrictor signaling and vessel contraction.Such regulatory changes may act to compensate for increased vasoconstrictor-induced vessel contraction.
Affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, United Kingdom; and email@example.com.Show MeSH
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Mentions: The extent of ET1- and UTP-induced PLC signaling desensitization was examined in MSMC transfected with eGFP-PH (0.5 μg) and loaded with the Ca2+-sensitive dye Fura-Red (4 μM, 60 min) to allow simultaneous measurement of changes in cellular IP3 and [Ca2+]i, using standard desensitization protocols (21, 22). For ET1, MSMC were challenged with a short desensitizing pulse of ET1 (50 nM, for 30 s, R1) followed by a wash period (5 min) and then a second ET1 challenge (50 nM, 30 s, R2). For cells prepared from 6-wk-old animals, initial ET1 challenge induced rapid, but transient translocations of eGFP-PH from the plasma membrane to the cytoplasm. Changes in eGFP-PH fluorescence were paralleled by changes in Fura-Red fluorescence, and responses returned to baseline within 5 min of agonist washout (Fig. 5, A and B). Changes in eGFP-PH and Fura-Red signals were reduced during a second (R2) ET1 challenge, indicative of diminished IP3 and Ca2+ increases in response to agonist re-challenge. For UTP, MSMC were challenged with a submaximal (approximate EC50) concentration of UTP (10 μM), for 30 s before (R1) and after (R2) addition of a maximal UTP concentration (100 μM, for 1 min, Rmax; to induce receptor desensitization). R2 values were attenuated compared with R1, indicating a desensitization of UTP-stimulated PLC signaling (Fig. 5, C and D).
Affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, United Kingdom; and firstname.lastname@example.org.