Urotensin-II (U-II), a peptide with multiple vascular effects, is detected in cholinergic neurons of the rat brainstem and spinal cord. Here, the effects of U-II on [Ca2+]i, was examined in dissociated rat spinal cord neurons by fura 2 microfluorimetry. The neurons investigated were choline acetyltransferase-positive and had morphological features of motoneurons. U-II induced [Ca2+]i, increases in these neurons with a threshold of 10-9 M, and a maximal effect at 10-6 M with an estimated EC50 of 6.2 × 10-9 M. The [Ca2+]i increase induced by U-II was mainly caused by Ca2+ influx from extracellular space, as the response was markedly attenuated in a Ca2+-free medium. Omega-conotoxin GVIA (10-7 M), a N-type Ca2+ channel blocker, largely inhibited these increases, whereas the P/Q Ca2+ channel blocker, omega-conotoxin GVIIC (10-7 M) and the L-type Ca2+ channel blocker, verapamil (10-5 M) had minimal effects. Down-regulation of protein kinase C by 4-α-phorbol 12-myristate 13-acetate (10-6 M) or enzyme inhibition using the specific inhibitor bisindolylmaleimide I (10-6 M) did not inhibit the observed effects. Similarly, inhibition of protein kinase G with KT5823 (10-6 M) or Rp-8-pCPT-cGMPS (3 × 10-5 M) did not modify U-II-induced [Ca2+]i increases. In contrast, protein kinase A inhibitors KT5720 (10-6 M) and Rp-cAMPS (3 × 10-5 M) reduced the response to 25 ± 3% and 42 ± 8%, respectively. Present results demonstrate that U-II modulates [Ca2+]i, in rat spinal cord neurons via protein kinase A cascade.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-20181 |
| Date | 01 November 2002 |
| Creators | Filipeanu, Catalin M., Brailoiu, Eugen, Le Dun, Siok, Dun, Nae J. |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | ETSU Faculty Works |
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