title: Inhibition of cell migration via G protein-coupled receptors to opioid peptides and angiotensin.
abstract: Neurotransmitters are stimulatory as well as inhibitory regulators of cell migration. Angiotensin is such an inhibitory regulator of the SDF-1-induced migration of cytotoxic T lymphocytes, as we have investigated by time-lapse videomicroscopy and computer-assisted cell tracking. For angiotensin II, the most effective form of angiotensin for the inhibition of migration, two G protein-coupled receptors are known, which both downregulate the activity of the adenylyl cyclase via activation of inhibitory G proteins. This downregulation of the enzymatic activity is a key signaling event for the inhibition of T lymphocyte and tumor cell migration, while stimulatory neurotransmitters--for example, norepinephrine--cause an activation of the adenylyl cyclase. Similar to angiotensin, the SDF-1-induced migration of cytotoxic T lymphocytes was inhibited by DAMGO, a specific agonist for the mu-opioid receptor, which is coupled to inhibitory G proteins, too. More interestingly, DAMGO downregulated the met-enkephalin-induced migration of MDA-MB-468 breast carcinoma cells. Met-enkephalin binds to the delta-opioid receptor and, with lower affinity, to the mu-opioid receptor. Since the delta-opioid receptor also activates inhibitory G proteins, the promigratory effect of met-enkephalin is caused by an intracellular signaling distinct from the engagement of each opioid receptor alone. In summary, the dual control of the adenylyl cyclase functions as an integrator of stimulatory and inhibitory signals for T lymphocyte and tumor cell migration, which are delivered by neurotransmitters and other signal substances that bind to G protein-coupled receptors.
authors.affiliation: Institute of Immunology, Witten/Herdecke University, Stockumer Str. 10, 58448 Witten, Germany. frankent@uni-wh.de
authors.forename: Frank
authors.initials: F
authors.lastname: Entschladen
authors.forename: Philipp
authors.initials: P
authors.lastname: Bastian
authors.forename: Bernd
authors.initials: B
authors.lastname: Niggemann
authors.forename: Kurt S
authors.initials: KS
authors.lastname: Zaenker
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lang
mesh_terms: D000809:Angiotensins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D018847:Opioid Peptides / Q000737:chemistry*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*; D011957:Receptors, Opioid / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D013997:Time Factors
chemical_list: D000809:Angiotensins; D018377:Neurotransmitter Agents; D018847:Opioid Peptides; D043562:Receptors, G-Protein-Coupled; D011957:Receptors, Opioid