Corticotropin releasing factor receptor-mediated stimulation of adenylate cyclase activity in the rat brain |
| |
| Authors: | F Mia Chen Louise M Bilezikjian Marilyn H Perrin Jean Rivier Wylie Vale |
| |
| Institution: | 1. Howard Hughes Medical Institute, and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA;2. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA;1. Department of Anatomy, University of California San Francisco, San Francisco, CA 94158, USA;2. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA;3. National Center for X-Ray Tomography, University of California San Francisco, San Francisco, CA 94158, USA;4. Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA;5. Program in Biomedical Sciences, University of California San Francisco, San Francisco, CA 94158, USA;6. Division of Biomedical Research, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Ioannina, Greece;7. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;8. Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA;9. Program in Neurosciences, University of California San Francisco, San Francisco, CA 94158, USA;10. Department of Physics, University of Jyväskylä, Jyväskylä 40014, Finland |
| |
| Abstract: | Corticotropin releasing factor (CRF)-stimulated adenylate cyclase activity and receptor binding were examined in rat brain homogenates using a potent synthetic CRF analog--D-Tyr3,D-Pro4,Nle18,21,alpha-helical]CRF3-41 (alpha-hel CRF3-41). Binding of alpha-hel CRF3-41 in the rat brain was saturable, reversible, of high affinity and exhibited relevant peptide specificity. This analog also stimulated adenylate cyclase activity of various brain regions; the greatest magnitude of stimulation was in the cerebral cortex followed by the septum, cerebellum and thalamus. Adenylate cyclase stimulation in the cerebral cortex was concentration-dependent with an ED50 of 2.5 +/- 0.4 nM for alpha-hel CRF3-41 and an ED50 of 16 +/- 2 nM for ovine and rat CRF. Maximal stimulation was comparable for all peptides. Agonist-stimulated adenylate cyclase activity was competitively blocked by the CRF antagonists. The inactive CRF analog, ovine CRF1-39, at concentrations less than 1 microM, did not significantly stimulate adenylate cyclase. Adrenalectomy, which has been reported to modulate CRF receptor number and CRF-stimulated adenylate cyclase activity in the anterior pituitary, had no effect on CRF receptor binding or CRF-stimulated adenylate cyclase activity in the cerebral cortex. These results suggest that, as in the anterior pituitary, at least some of the physiological responses mediated by CRF receptors in the brain utilize the cyclic nucleotide regulatory pathway as a post-receptor mechanism. |
| |
| Keywords: | corticotropin releasing factor (CRF) peptide receptor adenylate cyclase brain |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
