Activation of δ-Opioid Receptors Inhibits Neuronal-Like Calcium Channels and Distal Steps of Ca2+-Dependent Secretion in Human Small-Cell Lung Carcinoma Cells

• DOI: 10.1523/jneurosci.16-11-03672.1996
• Publication Date: 2018-04-03T22:35:16Z
• Authors: E. Sher; P. Cesare; A. Codignola; F. Clementi; P. Tarroni; A. Pollo; V. Magnelli; E. Carbone
• Keywords: Human lung; μ-opioid receptor

Human small-cell lung carcinoma (SCLC) cells express neuronal-like voltage-operated calcium channels (VOCCs) and release mitogenic hormones such as serotonin (5-HT). Opioid peptides, on the other hand, have been shown to reduce SCLC cell proliferation by an effective autocrine pathway. Here we show that in GLC8 cells, only delta-opioid receptor subtype mRNA is expressed. Consistently, selective agonist [D-Pen2-Pen5]-enkephalin (DPDPE), but not mu kappa agonists, potently dose-dependently inhibits high-threshold (HVA) VOCCs these cells. As peripheral neurons, this modulation largely voltage-dependent, mediated pertussis toxin (PTX)-sensitive G-proteins, cAMP-independent, mainly affecting N-type VOCCs. With same potency selectivity, DPDPE also antagonizes Ca(2+)-dependent of [3H]serotonin ([3H]5-HT) from However, depolarization-induced release, secretion induced thapsigargin or ionomycin. This suggests besides inhibiting HVA VOCCs, opioids exert a direct depressive action secretory apparatus latter effect PTX-sensitive G-protein but, contrary VOCC inhibition, it can be reversed elevations cAMP levels. These results for first time effectively depress both Ca2+ influx hormone using multiple modulatory pathways. It speculated two mechanisms may contribute opioid antimitogenic neuroendocrine