Mu and kappa opioid receptor expression in the mediobasal hypothalamus and effectiveness of selective antagonists on prolactin release during lactation

Abstract

Endogenous opioid peptides are involved in prolactin release during lactation, in part by decreasing tuberoinfundibular dopaminergic (TIDA) neuronal activity. Both μ and κ opioid receptors have a role in the suckling-induced prolactin rise after 4-5h pup deprivation. The aim of this study was to investigate effects of μ opioid receptor antagonist, β-funaltrexamine (β-FNA), and κ opioid receptor antagonist, nor-binaltorphimine (nor-BNI), on prolactin secretion and TIDA neuronal activity in lactating rats after 18h pup deprivation. After 4h separation from pups, the suckling-induced prolactin rise was abolished by 16 μg nor-BNI and 5 μg β-FNA, coincident with increased dihydroxyphenylacetic acid (DOPAC):dopamine ratio in the stalk-median eminence (SME). However, after 18h pups separation, these same doses of nor-BNI and β-FNA did not alter the prolactin surge or DOPAC:dopamine ratios in the SME. Higher doses of nor-BNI (32 μg) and β-FNA (10 μg) were required to inhibit suckling-induced prolactin secretion. β-FNA (10 μg) increased the DOPAC:dopamine ratio in the SME, whereas nor-BNI (32 μg) treatment had no effect. The μ and κ opioid receptor mRNA levels in the mediobasal hypothalamus were similar to suckled control rats after 4h pup deprivation, but increased 1.4-fold after 18h pup deprivation. These data support involvement of endogenous opioidergic systems in the suckling-induced prolactin rise after a prolonged (18h) period of pup deprivation, as well as the shorter (4h) pup deprivation period previously reported. Suppression of TIDA neuronal activity likely played a part in μ opioid receptor input to the suckling-induced prolactin rise after both 4h and 18h separation, whereas non-dopaminergic input was implicated with κ opioid receptors after 18h pup deprivation. Increased μ and κ opioid receptors gene expression in the mediobasal hypothalamus may contribute to reduced effectiveness of opioid receptor antagonists to block suckling-induced prolactin release after 18h pup deprivation.

The effects of <i>mu</i>-, <i>delta</i>- and <i>kappa</i>-opioid receptor activation on <i>in vitro</i> prolactin secretion by anterior pituitary cells of cyclic gilts

“…(Freeman et al, 2000;Dusza and Ciereszko, 2007;Ignacak et al, 2012). Endogenous opioid peptides (EOPs) are also involved in the regulation of prolactin secretion (Tavakoli-Nezhad and Arbogast, 2010;Vuong et al, 2010). They are products of proteolytic cleavage of protein precursors, i.e.…”

Promoting effects of isobavachin on neurogenesis of mouse embryonic stem cells were associated with protein prenylation

“…Small molecules for neuronal differentiation from mouse ES cells have received increasing attention as potential treatments for neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases [6,7] . However, there still remains a question about how small molecules direct and control the neuronal differentiation of mouse ES cells [8] . Recently, several small molecules have been reported to have neuronal differentiation ability.…”

“…However, the structurerelated neuronal differentiation mechanisms are still poorly understood. It is, therefore, important to identify the intrinsic or extrinsic factors that regulate the underlying molecular mechanisms involved in ES cell self-renewal, proliferation and neuronal differentiation [8] . Thus, isobavachin (IBA, Figure 1), Protein prenylation is a process of posttranslational modification present in a great number of proteins [10] .…”

“…The MAPK pathway regulates cell survival, proliferation, differentiation and motility [14,15] , such as the case of differentiation of mouse ES cells [15][16][17] . In the MAPK pathway, sustained activation or phosphorylation of extracellular signal-regulated kinase (ERK) is a specific requirement for the neural lineage commitment [8] and is associated with neuritis formation and neuron survival during ES cells differentiation [16] . In addition to ERK, p38MAPK phosphorylation is also activated during early mouse ES cell differentia tion [8,15] .…”

“…In the MAPK pathway, sustained activation or phosphorylation of extracellular signal-regulated kinase (ERK) is a specific requirement for the neural lineage commitment [8] and is associated with neuritis formation and neuron survival during ES cells differentiation [16] . In addition to ERK, p38MAPK phosphorylation is also activated during early mouse ES cell differentia tion [8,15] . This was proved to be a trigger in determining the ES cell differentiation fate [15] .…”