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Characterization of the relaxant action of urocortin, a new peptide related to corticotropin‐releasing factor in the rat isolated basilar artery
Author(s) -
Schilling L,
Kanzler Ch,
Schmiedek P,
Ehrenreich H
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702182
Subject(s) - urocortin , endocrinology , medicine , apamin , agonist , chemistry , potassium channel , receptor
1 In addition to its well established neuroendocrine and neurotransmitter effects, corticotropin releasing factor (CRF) exerts a potent vasorelaxant action. Recently, a CRF‐related peptide, urocortin, has been identified in the mammalian brain. In the present study, the cerebral vasomotor action of this peptide and the mechanism underlying its relaxant effect are characterized. 2 Ring segments obtained from the rat basilar artery were used for measurement of isometric force. The relaxant action of urocortin, CRF and sauvagine was studied in segments with a functionally intact endothelium. 3 In segments precontracted with prostaglandin F 2α , urocortin, CRF and sauvagine induced concentration‐related relaxation. The order of potency was as follows (pD 2 ±s.e.m. given in brackets): urocortin (9.32±0.07) > sauvagine (9.08±0.08) > CRF (7.50±0.07). Complete relaxation was achieved with each agonist. Relaxation was not affected by removal of the endothelium but was markedly attenuated in segments precontracted with 50 m m K + Krebs solution. The relaxant effect of urocortin was inhibited by astressin in an apparently competitive manner. A pA 2 value of 7.52 was estimated for astressin. Inhibition of urocortin‐induced relaxation was also observed in the presence of the adenylate cyclase inhibitor SQ22536 (pD 2 in the presence of 300 μ m SQ22536, 9.36±0.05) and the K + channel blockers tetraethylammonium (10 m m ; pD 2 , 8.65±0.07), iberiotoxin (100 n m ; pD 2 , 8.88±0.08) and apamin (10 n m ; pD 2 , 8.94±0.07). However, the inhibitory actions of SQ22536 and apamin or iberiotoxin were not additive. 4 The results suggest that urocortin induces relaxation of cerebral arteries by activating CRF‐R 2 receptors present in the vascular wall. Relaxation appears to be mediated by adenylate cyclase stimulation and activation of Ca 2+ ‐dependent K + channels.British Journal of Pharmacology (1998) 125 , 1164–1171; doi: 10.1038/sj.bjp.0702182