Effects of Neurogenic CGRP on Renal Afferent Peptidergic Neurons

Abstract

Although release of the proinflammatory vasodilator CGRP from peptidergic afferent nerves is generally unquestioned the matter is far less investigated with respect to afferent renal innvervation that is said to be involved in sympathetic control and blood pressure regulation. Furthermore, it is not known in how far released neurogenic CGRP will affect renal afferent innervation in return. Hence we wanted to test the hypothesis that CGRP elicits action potential production related to TRPV1 receptor stimulation in cultured neurons with afferent projections from the kidney in vivo.Cultured dorsal root ganglion neurons (Th11‐L2) of rats with renal afferents in vivo were investigated in current clamp mode to asses action potential generation or in voltage clamp mode to investigate inward currents during stimulation of TRPV1 receptors with acid of pH 6 (−80 mV holding voltage) and/or administration of CGRP (0,5 μmol). Furthermore, renal slices were incubated during baseline, experimental stimulation period and recovery to study CGRP release due to TRPV1 receptor stimulation (capsaicin 10−6 M, increased proton concentrations). CGRP concentrations in the organ bath were assessed with a commercial kit. Capsazepine was used for TRPV1 receptor blockadeMore than 90 DRG neurons with renal afferents were tested. Addition of CGRP did not change action potential generation nor inward currents. Proton stimulation (ph 6) of TRPV1 markedly increased long‐term inward currents (baseline −361,7 +/− 89,6 pA vs. −1393,3+/−337,3 pA, p<0,05, mean +/− SEM). The co‐stimulation of renal neurons with protons (pH 6) and CGRP led to an impairment of sustained inward current as compared to proton stimulation alone (baseline − 478,2 +/−54,4 pA vs. −767,6+/−89,6 pA, p<0,05, mean +/− SEM). Baseline CGRP release of renal slices (2.5 to 6 pg/ml) increased significantly after TRPV1 receptor stimulation (on average: 21+4 pg/ml CGRP).In contrast to our hypothesis CGRP could not elicit action potentials in afferent neurons related to the kidney but even impaired electric currents in general after TRPV1 receptor stimulation. Hence, renal CGRP secretion from peptidergic afferent nerves might decrease further neuronal CGRP release.Support or Funding InformationDFG Deutsche Forschungsgemeinschaft VE 104/4‐1This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.