Extensive co‐localization and heteromultimer formation of the vanilloid receptor‐like protein TRPV2 and the capsaicin receptor TRPV1 in the adult rat cerebral cortex

Abstract

The capsaicin receptor TRPV1, a member of the transient receptor potential (TRP) family of calcium-selective ion channels, responds to noxious stimuli and is predominantly expressed in nociceptive neurons. The homologous receptor TRPV2 shows wide tissue distribution including some sensory neurons, where it is proposed to function as a heat sensor or a growth-factor-activated channel. Members of the TRP family of channels have been shown to interact, resulting in hybrid channels with new properties. We examined the possibility of multimer formation between TRPV1 and TRPV2, using biochemical techniques. We present evidence that TRPV1 and TRPV2 can heteromultimerize efficiently in vitro. By using immunohistochemistry we detected co-localization of the two receptors in rat dorsal root ganglia. TRPC4 transcripts are also detected in capsaicin-sensitive dorsal root ganglia neurons. We extended the search for TRPV1-TRPV2 co-localization in the brain, where we detected extensive co-expression of the two receptors in the IV, V and VI layer neurons of the adult rat cerebral cortex. Co-immunoprecipitation experiments confirmed the interaction of the two receptors in vivo, indicating heteromultimer formation in native tissue. Formation of heteromultimers between vanilloid receptors may increase the functional diversity of this receptor family.

Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex

“…The TRPV1 antagonist capsazepine reversed the decline in 5-HT excitation induced by high WIN55,2212-2 doses. Interestingly, TRPV1 is expressed in both DR and PFC (Liapi and Wood, 2005) and is implicated in anxiety, conditioned fear, and hippocampal long-term potentiation (Marsch et al, 2007) and in schizophrenia (Chahl, 2007), whose negative symptoms overlap with depression. Second, we consider the possible role of the putative CB 3 R or a non-CB 1 cannabinoid receptor possessing a lower affinity to WIN55,212-2 proposed to be present in glutamatergic terminals and thus in a position to inhibit the release of excitatory amino acids (Hajos and Freund, 2002).…”

Integration of thermal and osmotic regulation of water homeostasis: the role of TRPV channels

“…Since receptors for both IGF-1 and insulin are expressed in SON (1, 9, 82), TRPV2 channels are viable candidates for mediating thermosensitivity. TRPV2 has been shown to form heteromeric complexes with TRPV1 (40,64). Thus formation of heteromeric channels with coexpressed osmosensitive TRPV1 and possibly TRPV4 channels in SON, OVLT, and SFO provides the potential for TRPV2 channels to participate in integration of osmotic and thermal signals for drinking as well as VP secretion.…”

Role of TRPV1 receptors in descending modulation of pain

“…Most research on the TRPV1 receptor's role in pain facilitation and pain transmission has been carried out at peripheral and spinal level (Nagy et al, 2004;Sasamura and Kuraishi, 1999). Nevertheless, data on the role of the TRPV1 receptor in the supraspinal control of pain is still scant, despite the fact that increasing evidence confirms the expression of TRPV1 receptors throughout the brain Liapi and Wood 2005;Maione et al, 2006;Mezey et al, 2000;Roberts et al, 2004;Sanchez et al, 2001;Toth et al, 2005). Increasing evidence demonstrates the presence of TRPV1 receptors throughout the periaqueductal gray (PAG) Maione et al, 2007;McGaraughty et al, 2003;Starowicz et al, 2007).…”

“…The TRPV1 receptor is localized in neuron cell bodies and dendrites, astrocytes and perivascular structures within the brain. (Liapi and Wood, 2005;Mezey et al, 2000;Roberts et al, 2004;Sasamura et al, 1998). At subcellular level TRPV1…”