Opioid-somatostatin interactions in regulating cancer cell growth

Abstract

Opioids and somatostatin mediate their cellular effects through specific membrane receptors. Three major receptor classes (delta, mu and kappa) were identified for opioids, while for somatostatin, five different receptor classes (SSTR1-5) have been cloned. Through the interaction with their receptors, opioids and somatostatin exert their effects on cell growth, proliferation, differentiation and secretion. Specific actions of each receptor type have been reported, to be implicated in one or more of the cell functions referred above but have been mainly correlated with cell growth control. In several systems the effect of either neuropeptide is the reverse, inducing cell growth rather than antiproliferative and proapoptotic signals. In recent years, a growing number of reports indicate a possible interaction between opioid and somatostatin system. This could occur at the receptor level, through a cross-interaction of either neuropeptide with either receptor type, or receptor hetero-dimerization, and at a post-receptor level, via interaction with specific signaling molecules. These interactions provide new directions for the identification of specific molecules acting at the receptor and post-receptor level, mimicking the effects of both categories of agents.

Neuronal differentiation of PC12 cells abolishes the expression of membrane androgen receptors

“…In this respect, elevation of intracellular Ca 2+ through membrane androgen receptors, in a specific time-dependent form, may prevent activation of catecholamine release by other cellular mechanisms. It is of note that similar results have been obtained in adrenomedullary cells following exposure to opioids which also increase intracellular Ca 2+ levels (reviewed in [65]), and as a result inhibit catecholamine secretion [66][67][68].…”

A novel bioactive peptide from yoghurts modulates expression of the gel-forming MUC2 mucin as well as population of goblet cells and Paneth cells along the small intestine

“…Special attention should be paid to the opioid sequence f114-119. Data from the literature have indeed shown that opioid peptides including α-casomorphins are able to interact with somatostatin receptors [46,47], which are also present on intestinal epithelial cells as well as on the parental HT29 cells. Somatostatin, synthesized and secreted by endocrine D cells of the stomach and intestine, is known to exert an inhibitory control in the gut.…”

The somatostatin receptor 4 agonist J-2156 reduces mechanosensitivity of peripheral nerve afferents and spinal neurons in an inflammatory pain model

“…Since J-2156 does not bind per se mu-opiod receptors (Ki 410 μM) this effect can only be explained by an intracellular signaling pathway. Potential interactions of SST receptors with opioid receptors have been suggested (Betoin et al, 1994;Hatzoglou et al, 2005;Maurer et al, 1982;Pfeiffer et al, 2002;Prinster et al, 2005). A recent study showed, that SSTR4 and delta-opioid receptors exist in a heteromeric complex in the spinal cord and function in synergistic manner (Somvanshi and Kumar, 2014).…”