P99	The vasorelaxing effect of Tuberoinfundibularpeptide of 39 residues (TIP39) in the coronary system of the rat depends on nitric oxide (NO) and a desensitisation of the cardiac PTH1-receptor.
G.Ross, M.Heinemann, K-D.Schlüter
Physilogisches Institut, Gießen, DE.

TIP39 is a member of the parathyroid hormone family and is known as an inotropic agent in the rat heart. This effect is mediated by the parathyroid hormone receptor-type 2 (PTH2r). The aim of this study was to investigate a possible influence of TIP39 on coronary resistance and its possible cross-reactivity with the parathyroid hormone receptor type 1 (PTH1r). Methods: Rat hearts were perfused in the Langendorff mode under pressure constant conditions. Changes in coronary resistance were investigated by analysing flow rates. Results: Under basal conditions TIP39 (100 nmol/l) showed no influence on coronary flow (basal 5.6±0.7 ml/min; TIP39 5.6±0.4 ml/min). However, after desensitisation of the cardiac PTH1r by the receptor agonist Ile5,Trp23,Tyr36-Parathyroid hormone-related peptide (Ile5-PTHrP, 100 nmol/l), TIP39 increased coronary flow from 3.5±0.3 ml/min to 4.3±0.3 ml/min. Under ischemic conditions endogenous PTHrP accumulates in rat hearts and this may desensitise the PTH1r. In post-ischemic hearts TIP39 increased coronary flow (control 5.0±1.0 ml/min; TIP39 6.9±1.3 ml/min). To investigate whether the vasodilative effect of TIP39 is NO-dependent, NO formation was inhibited by L-nitro arginine (L-NA, 100 µmol/l). In experiments in which the PTH1r was desensitised by exogenous Ile5-PTHrP or during ischemia by endogenous PTHrP, TIP39 was unable to increase coronary flow in co-presence of L-NA any longer (Ile5-PTHrP: control 3.3±0.5 ml/min, TIP39 3.2±0.5; endogenous PTHrP: control 3.7±0.9 ml/min, TIP39 3.9±1.0 ml/min). Conclusion: The results suggest a cross-talk between the PTH1r and the PTH2r in coronary circulation of the rat. It seems that the PTH1r normally blocks an activation of the PTH2r by TIP39. Desensitisation of the PTH1r abolishes this blockade and TIP39 could increase coronary flow. Furthermore the results let assume, that TIP39 mediates this effect by generation of NO.

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