Identification of neuropeptide receptors expressed by melanin‐concentrating hormone neurons

Abstract

Melanin-concentrating Hormone (MCH) is a 19 amino acid cyclic neuropeptide that acts in rodents via the MCH receptor 1 (MCHR1) to regulate a wide variety of physiological functions. MCH is produced by a distinct population of neurons located in the lateral hypothalamus (LH) and zona incerta (ZI) but MCHR1 mRNA is widely expressed throughout the brain. The physiological responses and behaviors regulated by the MCH system have been investigated, but less is known about how MCH neurons are regulated. The effects of most classical neurotransmitters on MCH neurons have been studied, but those of neuropeptides are poorly understood. In order to gain insight into how neuropeptides regulate the MCH system, we investigated which neuropeptide receptors are expressed by MCH neurons using double in situ hybridization. In all, twenty receptors, selected based upon either a suspected interaction with the MCH system or demonstrated high expression levels in the LH and ZI, were tested to determine whether they are expressed by MCH neurons. Overall, eleven neuropeptide receptors were found to exhibit significant colocalization with MCH neurons: Nociceptin / Orphanin FQ Opioid receptor (NOP), MCHR1, both Orexin receptors (ORX), Somatostatin receptor 1 and 2 (SSTR1, SSTR2), the Kisspeptin receotor (KissR1), Neurotensin receptor 1 (NTSR1), Neuropeptide S receptor (NPSR), Cholecystokinin receptor A (CCKAR) and the κ-opioid receptor (KOR). Of these receptors, six have never before been linked to the MCH system. Surprisingly, several receptors thought to regulate MCH neurons displayed minimal colocalization with MCH, suggesting that they may not directly regulate the MCH system.

Melanin-Concentrating Hormone acts through hypothalamic kappa opioid system and p70S6K to stimulate acute food intake

“…The presence of k-OR in MCH neurons indicates that the activity of MCH neurons is also regulated by endogenous opioid-neurons. In fact it is known that dynorphin neurons are co-localized with MCHR1 neurons (Chee et al 2013) and that k-OR is co-localized with MCH neurons (Parks et al, 2014). These anatomical and biochemical findings imply strong functional relationships between the two systems.…”

The Melanin-Concentrating Hormone as an Integrative Peptide Driving Motivated Behaviors

“…The application of Dyn or N/OFQ hyperpolarizes MCH cells, increasing their input resistance (Li and van den Pol, 2006; Parsons and Hirasawa, 2011), probably through κ-opioid (κOR) and NOP receptors present in these cells (Parks et al, 2014) ( Figure 4B ). These results suggest that MCH neurons could potentially be stimulated by ORX and inhibited by Dyn and N/OFQ originated from the same fibers.…”

Neurons containing orexin or melanin concentrating hormone reciprocally regulate wake and sleep

“…Overall, MCH neurons project to the same targets as orexin neurons (Bittencourt and Elias, 1993 , 1998 ; Elias and Bittencourt, 1997 ; Elias et al, 2008 ). MCH neurons have been shown by in situ hybridization, to co-localize with nociceptin/orphanin FQ opioid receptor (NOP), MCHR1, both orexin receptors (ORX), somatostatin receptors 1 and 2 (SSTR1, SSTR2), kisspeptin receptor (KissR1), neurotensin receptor 1 (NTSR1), neuropeptide S receptor (NPSR), cholecystokinin receptor A (CCKAR), and the κ-opioid receptor (Parks et al, 2014b ).…”