A5662 Effects of Neurogenic CGRP on Renal Afferent Peptidergic Neurons

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Objectives: Although release of the proinflammatory vasodilator CGRP from peptidergic afferent nerves is unquestioned it is not known if released neurogenic CGRP will affect renal afferent innervation in return thus influencing sympathetic activity e.g. in hypertension. Hence we wanted to test the hypothesis that CGRP elicits action potential production related to TRPV1 receptor stimulation in cultured renal neurons. Methods: Cultured dorsal root ganglion neurons (Th11-L2) of rats with renal afferents 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 to study CGRP release due to TRPV1 receptor stimulation. (CGRP concentrations assessed in organ bath). Results: More 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 impaired sustained inward current as compared to proton stimulation alone (baseline −478,2 +/−54,4 pA vs. −767,6+/−89,6* pA, p < 0,05). CGRP release of renal slices increased significantly after TRPV1 receptor stimulation (on average: 21+/−4 pg/ml CGRP). Conclusion: 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.