TIP39 is a member of the parathyroid hormone family and a high specific ligand of the PTH-2 receptor (PTH-2r). The aim of this study was to investigate the influence of TIP39 on coronary resistance (CR) and a possible crosstalk between vascular PTH-receptors in the cardiovascular system. Isolated rat hearts were perfused under pressure constant conditions (Langendorff) and the coronary flow was determinated. Under basal conditions TIP39 showed no influence on CR. But if hearts were pre-treated with a PTH-1r agonist, a following application of TIP39 reduced CR (22%). This effect was abolished either in co-presence of a PTH-2r antagonist or by using a PTH-1r antagonist for pre-treatment instead of the PTH-1r agonist. In an ischemia-reperfusion model PTHrP-receptors were desensitised during reperfusion and pre-ischemic addition of TIP39 reduced post-ischemic CR by 28%. In co-presence of the PTH-2r antagonist this effect was completely abolished again. Co-presence of L-nitro arginine for inhibition of NO-formation, abolished the TIP39 effect in both cases (exogenous and endogenous PTHrP). In conclusion it seems, that under normoxic conditions the PTH-1r blocks an activation of the PTH-2r by TIP39. Under hypoxic conditions the PTH-1r seems to be desensitised by endogenous PTHrP. Now, TIP39 can reduce the CR in a NO dependent manner.