Trpv1 Reporter Mice Reveal Highly Restricted Brain Distribution and Functional Expression in Arteriolar Smooth Muscle Cells

Department of Anatomy, University of San Francisco, San Francisco, California 94158, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 03/2011; 31(13):5067-77. DOI: 10.1523/JNEUROSCI.6451-10.2011
Source: PubMed


The heat and capsaicin receptor, TRPV1, is required for the detection of painful heat by primary afferent pain fibers (nociceptors), but the extent to which functional TRPV1 channels are expressed in the CNS is debated. Because previous evidence is based primarily on indirect physiological responses to capsaicin, here we genetically modified the Trpv1 locus to reveal, with excellent sensitivity and specificity, the distribution of TRPV1 in all neuronal and non-neuronal tissues. In contrast to reports of widespread and robust expression in the CNS, we find that neuronal TRPV1 is primarily restricted to nociceptors in primary sensory ganglia, with minimal expression in a few discrete brain regions, most notably in a contiguous band of cells within and adjacent to the caudal hypothalamus. We confirm hypothalamic expression in the mouse using several complementary approaches, including in situ hybridization, calcium imaging, and electrophysiological recordings. Additional in situ hybridization experiments in rat, monkey, and human brain demonstrate that the restricted expression of TRPV1 in the CNS is conserved across species. Outside of the CNS, we find TRPV1 expression in a subset of arteriolar smooth muscle cells within thermoregulatory tissues. Here, capsaicin increases calcium uptake and induces vasoconstriction, an effect that likely counteracts the vasodilation produced by activation of neuronal TRPV1.

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    • "Whereas activation of CB1 receptors inhibits adenylate cyclase, reducing neurotransmitter release (Vaughan et al., 2000), activation of TRPV1 receptors promotes membrane depolarization, increasing the firing rate (Xing and Li, 2007). Both CB1 and TRPV1 receptors are widely expressed in brain areas involved in anxiety and fear, such as the medial pre-frontal cortex, hippocampus, hypothalamus and midbrain periaqueductal gray (PAG) (Cavanaugh et al., 2011; Mezey et al., 2000; Tsou et al., 1998). The PAG is a mesencephalic brain region divided along its rostroecaudal axis into dorsomedial, dorsolateral (dlPAG), lateral and ventrolateral columns. "
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    • "The role—and indeed the very presence—of TRPV1 in vascular tissue remain highly contentious. While several groups have reported evidence of endothelial TRPV1 expression (Bratz et al. 2008; Fantozzi et al. 2003; Yang et al. 2010), others have failed to reproduce these findings (Cavanaugh et al. 2011; Marrelli et al. 2007). Many studies have relied on mRNA expression alone, and protein quantification has often been conducted in the absence of appropriate controls, or using antibodies that have not been validated in TRPV1 knockout (KO) tissue. "

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