Transient receptor potential vanilloid type 1 channels act as mechanoreceptors and cause substance P release and sensory activation in rat kidneys

Abstract

Stimulation of capsaicin receptors results in an increase in afferent renal nerve activity (ARNA), but it is unclear how capsaicin contributes to sensory activation intrarenally. Here, we studied the relationships between capsaicin receptor activation, substance P (SP) release, and the sensory response in the rat renal pelvis. Immunoblots showed that one of the capsaicin receptors, transient receptor potential vanilloid type 1 channel (TRPV1), was found in various renal tissues and was especially abundant in the renal pelvis, where most sensory nerve fibers originate. Interestingly, immunolabeling showed colocalization of TRPV1, SP, and the panneuronal marker PGP9.5 in the renal pelvis. Electrophysiological recordings showed that SP and capsaicin activated the same mechanosensitive ARNA in a single-unit preparation. Intrapelvic administration of capsaicin or a specific TRPV1 agonist, resiniferatoxin, resulted in a dose-dependent increase in multi-unit ARNA and SP release, and these effects were blocked by the TRVP1 blocker capsazepine. Inhibition of the SP receptor by L-703,606 largely prevented capsaicin- or resiniferatoxin-induced ARNA. Capsazepine also prevented intrapelvic pressure (IPP)-dependent ARNA activation and contralateral diuresis/natriuresis in the renorenal reflex at an IPP of 20 mmHg, but had no effect at an IPP of 50 mmHg. These data indicate that TRPV1, a low-pressure baroreceptor, is present in the renal pelvis and exclusively regulates neuropeptide release from primary renal afferent C-fibers in response to mechanostimulation.

Preventive Effect of SA13353, a Novel Transient Receptor Potential Vanilloid 1 Agonist, on Ischemia/Reperfusion-Induced Renal Injury in Rats

“…It has been demonstrated most recently that TRPV1 protein is highly present in the renal pelvis and exclusively regulates neuropeptide release from primary renal afferent nerves in response to mechanostimulation [19]. Moreover, TRPV1 protein is abundantly located in renal tubules of medulla, although its functional roles are unknown [19]. The renal medulla contains nephron segments that are most susceptible to ischemic injury [20].…”

Mechanosensitive N -Methyl- d -Aspartate Receptors Contribute to Sensory Activation in the Rat Renal Pelvis

“…3 The reason for the absence of NMDA1 mRNA is not known. However, Washbourne et al 24 showed that NMDAR subunits are present in mobile transport packets and move rapidly along microtubules to axodendritic sites during synaptogenesis in rat cortical neurons.…”

“…3,19 Western blotting was performed using antibodies (Santa Cruz) against rat NMDA1 (1:1000), serine racemase (SR) (1:1000), or actin (1:2000) as described previously. 3,8 -10 The negative control was staining with primary antibody preincubated with specific blocking peptide (Santa Cruz).…”

“…3 A PE-10 catheter with a fine tip was inserted into the left renal artery via the abdominal aorta and left femoral artery for intrarenal arterial (i.r.a.) infusion at a rate of 0.48 mL h Ϫ1 .…”

“…1,2 Mechanically stimulating renal receptors through an increase in intrapelvic pressure (IPP) causes the release of sensory neuropeptides, such as substance P (SP), with consequent activation of afferent renal nerves. [3][4][5][6][7][8][9][10] Increases in afferent renal nerve activity (ARNA) evoke an inhibitory renorenal reflex, which causes diuresis and natriuresis as a result of a reflex withdrawal of efferent renal sympathetic nerve activity. [3][4][5][6][7][8][9][10] This reflex is seen not only when stimuli are directly applied to the kidney, but also during acute fluid expansion.…”