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Tuberoinfundibular Peptide of 39 Residues: A New Mediator of Cardiac Function via Nitric Oxide Production in the Rat Heart
- Source :
- Endocrinology. 146:2221-2228
- Publication Year :
- 2005
- Publisher :
- The Endocrine Society, 2005.
-
Abstract
- Tuberoinfundibular peptide (TIP39) was initially identified as a neurotransmitter and agonist of the PTH2 receptor, which is expressed in the cardiovascular system. This study documents for the first time the cardiac expression and function of TIP39. Expression was analyzed via RT-PCR. Function was characterized on Langendorff-perfused rat hearts as left ventricular developed pressure (LVDP) and on isolated cells via a cell edge detection system. cGMP levels were detected with RIA. Tuberoinfundibular peptide (TIP39) mRNA was found to be constitutively expressed in coronary endothelium cells, isolated cardiomyocytes, ventricles, atria, and aorta. At first we investigated the vasodilatory properties of TIP39 (100 nM) in the presence of L-nitro-arginine (L-NA, 100 microM). Surprisingly, TIP39 had no vasodilatory effect but decreased LVDP by 35 +/- 7%. In the absence of L-NA, addition of TIP39 decreased LVDP by 8 +/- 2%. The PTH2 receptor antagonist Trp23-Tyr36-PTHrP (1-36, 100 nM) abolished this TIP39 effect in the presence of L-NA. The experiments with isolated cardiomyocytes provided similar results. TIP39 (10 nM) lowered the contraction amplitude by 6 +/- 3%. In the presence of L-NA (100 micromol/liter), TIP39 lowered the amplitude by 34 +/- 6%. cGMP concentration in cardiomyocytes was stimulated by TIP39 (10 nM) in the same range as by the nitric oxide (NO) donor SNAP (100 microM). In the presence of L-NA, this increase was abolished. These results suggest that an inhibition of endogenous NO production unmasks a profound negative inotropic effect of TIP39 that is mediated by an activation of the PTH2 receptor. The results obtained with isolated cardiomyocytes suggest that myocyte-derived NO, rather than vascular NO, is responsible for this effect. cGMP seems to be the downstream signal of produced NO.
- Subjects :
- Male
Agonist
medicine.medical_specialty
medicine.drug_class
Heart Ventricles
Gene Expression
Vasodilation
Biology
Nitric Oxide
Nitroarginine
Nitric oxide
Receptor, Parathyroid Hormone, Type 2
chemistry.chemical_compound
Endocrinology
Internal medicine
Pressure
medicine
Animals
Nitric Oxide Donors
Enzyme Inhibitors
Rats, Wistar
Receptor
Neurotransmitter
Cyclic GMP
Aorta
Cells, Cultured
Reverse Transcriptase Polymerase Chain Reaction
Neuropeptides
Snap
Heart
Receptor antagonist
Coronary Vessels
Myocardial Contraction
Rats
medicine.anatomical_structure
chemistry
Depression, Chemical
Tuberoinfundibular pathway
Nitric Oxide Synthase
Subjects
Details
- ISSN :
- 19457170 and 00137227
- Volume :
- 146
- Database :
- OpenAIRE
- Journal :
- Endocrinology
- Accession number :
- edsair.doi.dedup.....1b26e2eacf037a0a30038fa6c5a58168