Colocalization and shared distribution of endomorphins with substance P, calcitonin gene‐related peptide, γ‐aminobutyric acid, and the mu opioid receptor

Abstract

The endomorphins are endogenous opioids with high affinity and selectivity for the mu opioid receptor (MOR, MOR-1, MOP). Endomorphin-1 (Tyr-Pro-Trp-Phe-NH(2); EM1) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2); EM2) have been localized to many regions of the central nervous system (CNS), including those that regulate antinociception, autonomic function, and reward. Colocalization or shared distribution (overlap) of two neurotransmitters, or a transmitter and its cognate receptor, may imply an interaction of these elements in the regulation of functions mediated in that region. For example, previous evidence of colocalization of EM2 with substance P (SP), calcitonin gene-related peptide (CGRP), and MOR in primary afferent neurons suggested an interaction of these peptides in pain modulation. We therefore investigated the colocalization of EM1 and EM2 with SP, CGRP, and MOR in other areas of the CNS. EM2 was colocalized with SP and CGRP in the nucleus of the solitary tract (NTS) and with SP, CGRP and MOR in the parabrachial nucleus. Several areas in which EM1 and EM2 showed extensive shared distributions, but no detectable colocalization with other signaling molecules, are also described.

Decreased Endomorphin-2 and μ-Opioid Receptor in the Spinal Cord Are Associated with Painful Diabetic Neuropathy

“…Our results indicate that, similar to EM2 distribution, the expression of MOR was concentrated in the superficial layer of the spinal dorsal horn (Zadina et al, 1997; Wang et al, 2003; Greenwell et al, 2007). In diabetic rats, our immunohistochemistry analyses provided evidence that the expression of MOR was reduced significantly, along with the decrease in EM2 expression in the spinal dorsal horn, indicating that MOR may be involved in antinociception produced by EM2 in PDN.…”

Brain neuropeptides in gastric mucosal protection

“…In addition, interaction between TRH and leptin in the DVC was described where TRH1 and leptin receptors are co-localized [40]. Furthermore, CCK was shown to activate orexin and neurotensin neurons [41], endomorphin-2 is co-localized with SP and CGRP in the NTS [42] and the peripherally (i.v.) given neurotensin may induce gastroprotection by activating the central endocannabinoid system [43].…”

Effects of Anesthetics, Sedatives, and Opioids on Ventilatory Control

“…Opioid receptors are widely distributed in the spinal cord (735), the central nervous system (CNS) (93,130,223,227,407,408,465,527,542,633,733,734), including the respiratory nuclei (242,357,389,390,466,594), and the peripheral nervous system including the peripheral chemoreceptors (337). The role of endogenous opiates in the control of respiration remains ill defined (241,597) compared to the wellknown respiratory depressant effects of μ-opioid agonists in clinical use.…”