Journal article

Vasodilatory effect of tuberoinfundibular peptide (TIP39):: Requirement of receptor desensitization and its beneficial effect in the post-ischemic heart


Authors listRoss, Guenter; Heinemann, Marcus P.; Schlueter, Klaus-Dieter

Publication year2007

Pages878-886

JournalPeptides

Volume number28

Issue number4

ISSN0196-9781

DOI Linkhttps://doi.org/10.1016/j.peptides.2006.12.010

PublisherElsevier


Abstract
Tuberoinfundibular peptide of 39 residues (TIP39) is a member of the parathyroid hormone (PTH) family and a highly specific ligand of the PTH-receptor type 2 (PTH-2r). Recent studies have shown vasoactive properties of TIP39 in the kidney. This effect was stronger after desensitization of the parathyroid hormone-receptor type 1 (PTH-1r). The aims of our study were three-fold: (1) to investigate the influence of TIP39 on coronary resistance (CR), (2) to investigate a possible cross-talk between vascular PTH-receptors in the cardiovascular system, and (3) to investigate whether the endogenously released PTHrP during ischemia induces such a desensitizing effect. Experiments were performed on isolated rat hearts that were perfused with a constant pressure (Langendorff mode) and the coronary flow was determined. Under basal conditions, TIP39 showed no influences on CR. However, TIP39 reduced the CR by approximately 22% after pre-treatment of the hearts with a PTH-1r agonist. This TIP39 effect was abolished either by co-administration of a PTH-2r antagonist or by inhibition of nitric oxide (NO) formation. In an ischemia-reperfusion model endogenously released PTHrP desensitized the PTH-1r and pre-ischemic addition of TIP39 reduced post-ischemic CR by about 28%. Again, this effect was completely abolished in the presence of the PTH-2r antagonist or the PTH-1r-antagonist or by inhibition of NO formation. However, no effect was observed when TIP39 was washed-out prior to ischemia or if the treatment with TIP39 was restricted to the reperfusion. Furthermore, a pre-ischemic application of the NO-dependent vasorelaxant bradykinin provoked a similar effect on the post-ischemic CR than TIP39. In conclusion, a NO-dependent vasodilatory effect of TIP39 was demonstrated if the PTH-1r is desensitized by either exogenously applicated PTHrP peptides or endogenously released PTHrP. (c) 2007 Published by Elsevier Inc.



Citation Styles

Harvard Citation styleRoss, G., Heinemann, M. and Schlueter, K. (2007) Vasodilatory effect of tuberoinfundibular peptide (TIP39):: Requirement of receptor desensitization and its beneficial effect in the post-ischemic heart, Peptides, 28(4), pp. 878-886. https://doi.org/10.1016/j.peptides.2006.12.010

APA Citation styleRoss, G., Heinemann, M., & Schlueter, K. (2007). Vasodilatory effect of tuberoinfundibular peptide (TIP39):: Requirement of receptor desensitization and its beneficial effect in the post-ischemic heart. Peptides. 28(4), 878-886. https://doi.org/10.1016/j.peptides.2006.12.010



Keywords


39 RESIDUESCORONARY ENDOTHELIAL-CELLScoronary systemHORMONE-RELATED PROTEINISCHEMIA-REPERFUSION INJURYKINASE-CMESSENGER-RIBONUCLEIC-ACIDparathyroid hormonePARATHYROID-HORMONEparathyroid hormone-related proteinRAT-HEARTVASCULAR SMOOTH-MUSCLEvasodilatory peptides

Last updated on 2025-02-04 at 03:45