Document Detail

Protein kinase Cs and tyrosine kinases in permissive action of prostacyclin on cerebrovascular regulation in newborn pigs.
MedLine Citation:
PMID:  8979294     Owner:  NLM     Status:  MEDLINE    
The involvement of protein kinase C (PKC) and protein tyrosine kinase (PTK) in hypercapnia-induced cerebral vasodilation in newborn pigs was investigated with closed cranial windows using the PKC stimulator phorbol 12-myristate 13-acetate (PMA), and the PTK inhibitors, genistein and herbimycin A. The influence of prostaglandin I2 was eliminated using the prostaglandin cyclooxygenase inhibitor, indomethacin. Changes in pial arteriolar diameters in response to hypercapnia [partial pressure of arterial CO2 approximately 9.3 kPa (70 torr)] were analyzed. Genistein (40 micrograms/mL), herbimycin A (10 microM), or PMA (1 microM) did not affect cerebral vasodilation to hypercapnia when applied topically. Indomethacin (5 mg/kg i.v.) treatment blocked the dilation to hypercapnia and attenuated hypercapnia-induced increase in cortical cAMP. Genistein and herbimycin A restored the response to hypercapnia to indomethacin-treated piglets. PMA also restored the pial arteriolar dilation and the cAMP response to hypercapnia to indomethacin-treated piglets. One-hour exposure to 10 microM PMA, to down-regulate PKC, blocked vasodilation to hypercapnia but did not inhibit vasodilation to sodium nitroprusside. After prolonged (2 h) topical exposure of indomethacin-treated piglets to 10 microM PMA, neither genistein nor iloprost could restore dilation to hypercapnia. These results indicate that PKC stimulation and/or PTK inhibition may permit hypercapnia-induced vasodilation. These data further suggest that PKC is downstream from PTK in the regulatory pathway. Because previous data showed prostaglandin I2 at subdilator concentrations can also return dilation to hypercapnia to piglets treated with indomethacin, prostaglandin I2 could provide its permissive input by activating PKC and/or inhibiting PTK.
G P Rama; H Parfenova; C W Leffler
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Pediatric research     Volume:  41     ISSN:  0031-3998     ISO Abbreviation:  Pediatr. Res.     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-03-18     Completed Date:  1997-03-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  83-9     Citation Subset:  IM    
Department of Physiology/Biophysics, University of Tennessee, Memphis 38163, USA.
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MeSH Terms
Animals, Newborn
Antihypertensive Agents / pharmacology*
Arterioles / drug effects
Epoprostenol / pharmacology*
Hypercapnia / physiopathology
Isoflavones / pharmacology
Lactams, Macrocyclic
Pia Mater / blood supply*,  drug effects
Protein Kinase C / metabolism*
Protein-Tyrosine Kinases / metabolism*
Quinones / pharmacology
Tetradecanoylphorbol Acetate / pharmacology
Vasodilation / physiology*
Grant Support
Reg. No./Substance:
0/Antihypertensive Agents; 0/Benzoquinones; 0/Isoflavones; 0/Lactams, Macrocyclic; 0/Quinones; 16561-29-8/Tetradecanoylphorbol Acetate; 35121-78-9/Epoprostenol; 446-72-0/Genistein; 70563-58-5/herbimycin; EC Kinases; EC Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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