Adrenomedullin and the calcitonin receptor-like receptor system mRNA expressions in the rat heart and sensory ganglia in experimentally-induced long-term diabetes

Abstract

Both adrenomedullin and calcitonin gene-related peptide (CGRP) regulate vascular tone in the heart, being cardioprotective in hypoxia. Additionally, adrenomedullin exhibits antiproliferative and antiapoptotic functions in the myocardium, while CGRP exerts positive chronotropic effect. Their actions are mediated through the specific G protein-coupled receptor, CRLR, whose ligand affinity is determined by receptor activity modifying proteins RAMP1-3. CGRP binds to the complex formed by CRLR/RAMP1, whereas CRLR/RAMP2 and CRLR/RAMP3 serve as receptors for adrenomedullin. Here, we quantified expression of this signaling system in the rat heart and supplying sensory ganglia (dorsal root ganglia T1-T4 and vagal nodose ganglia) in streptozotocin-induced diabetes. In the course of diabetes, an increase of CRLR mRNA was noticed in the right ventricle 8 weeks and of RAMP3 mRNA in the left ventricle and right atrium 26 weeks after induction of diabetes. Relative expressions of other tested genes were not significantly altered. In the nodose vagal supplying specific cardiac afferents, but not in dorsal root ganglia which provide cardiac pain fibres, a small upregulation of CGRP expression was detected. In summary, the shifts observed in diabetes may favour a trend of a pronounced adrenomedullin signaling. These observations may provide a new possible therapeutic strategy for diabetic cardiomyopathy.

Calcitonin gene-related peptide protects rats from cerebral ischemia/reperfusion injury via a mechanism of action in the MAPK pathway

“…CGRP is a polypeptide composed of 37 amino acids, and it is extensively expressed in the central and peripheral nervous systems. Currently, CGRP is considered the most potent vasodilator ( 10 , 11 ). CGRP serves a protective function in brain tissues.…”

Regulation of Prepro-NeuropeptideW/B and Its Receptor in the Heart of ZDF Rats: An Animal Model of Type II DM

“…Cardiac spinal afferents convey nociceptive sensory information from the heart to the spinal cord throughout DRG, which are located in the nerve cell bodies of these sensory neurons [ 17 ]. These cardiac sensory fibers release different neuromediators, including calcitonin-gene-related peptide and/or substance P [ 8 ]. Results of our IF experiments demonstrated the presence of NPB in some of the neuronal bodies and nerve fibers but the absence of NPW in DRG.…”

“…The activity of the sympathetic part of cardiac innervation is increased in individuals with DM, while the activity of the parasympathetic nervous system in the heart of these individuals decreases [ 2 ]. In the diabetic heart, in addition to the signaling systems of classical neurotransmitters, the signaling systems of various neuropeptides are also more or less affected including, e.g., neuropeptide Y [ 3 , 4 , 5 ], vasoactive intestinal polypeptide [ 6 ], substance P [ 4 , 7 ], and calcitonin gene-related peptide [ 8 , 9 , 10 ], suggesting impairment of whole intracardiac nervous system. This impairment contributes to the cardiac dysfunction and heart failure associated with DM [ 11 ].…”