CRF2 receptors are highly expressed in the human cardiovascular system and their cognate ligands urocortins 2 and 3 are potent vasodilators

British Journal of Pharmacology
Katherine E Wiley, Anthony P Davenport

Abstract

1. Systemic infusions of urocortin 1 produce a decrease in mean arterial pressure. This effect may be mediated by a direct action on novel corticotropin-releasing factor type 2 (CRF(2)) receptors predicted to be expressed in blood vessels and the heart. Our objectives were to determine the presence of CRF(2) receptors in the human cardiovascular system using the selective radioligand [(125)I]antisauvagine 30. We also investigated the potential functional roles of novel CRF(2) ligands in the regulation of vascular tone in human arteries in vitro. 2. Radioligand binding techniques were used to characterise the CRF(2) receptor. [(125)I]antisauvagine 30 bound specifically, saturably, reversibly and with high affinity to CRF(2) receptors in human left ventricle (K(D) 0.21+/-0.03 nm, B(MAX) 0.80+/-0.18 fmol mg(-1) protein), and no change in receptor density or affinity was observed in the dilated cardiomyopathy group. 3. Autoradiographical studies revealed highly localised binding of [(125)I]antisauvagine 30 to intramyocardial blood vessels. Binding sites were also detected in the myocardium and in the medial layer of internal mammary arteries. 4. In endothelium-denuded human internal mammary artery in vitro, all peptides tested prod...Continue Reading

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