Opposing actions of the EGF family and opioids: heparin binding-epidermal growth factor (HB-EGF) protects mouse cerebellar neuroblasts against the antiproliferative effect of morphine.
Endogenous opioids and opiate drugs of abuse inhibit the proliferation of cerebellar external granular layer (EGL) neuroblasts by mechanisms that are incompletely understood. Opioids do not act alone, rather multiple extracellular factors regulate granule cell neurogenesis and these undoubtedly act in concert with opioids to shape developmental outcome. We examined whether, heparin binding-epidermal growth factor-like growth factor (HB-EGF), a recently described member of the epidermal growth factor (EGF) family, might compete with an inhibitory opioid signal. The results confirmed our ongoing studies that morphine inhibited neuroblast proliferation, while HB-EGF enhanced cell replication. HB-EGF not only counteracted the antiproliferative morphine signal, but invariably enhanced DNA synthesis irrespective of morphine treatment. Our findings suggest that regional and temporal differences in the availability of endogenous HB-EGF may serve to limit the response of EGL neuroblasts to opioids, and HB-EGF may be neuroprotective in opiate drug abuse. If similar responses occur in vivo, then the EGF family and the opioid system may represent distinct and contrasting components of an extracellular signaling system serving to coordinate EGL neurogenesis.
Opanashuk
L A
LA
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536-0084, USA.
Hauser
K F
KF
D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004247:DNA / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology
C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D009294:Narcotics; D004815:Epidermal Growth Factor; D009020:Morphine; D004247:DNA