Protein kinase Cs and tyrosine kinases in permissive action of prostacyclin on cerebrovascular regulation in newborn pigs. 1997

G P Rama, and H Parfenova, and C W Leffler
Department of Physiology/Biophysics, University of Tennessee, Memphis 38163, USA.

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.

UI MeSH Term Description Entries
D007529 Isoflavones 3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. 3-Benzylchroman-4-One,3-Benzylidene-4-Chromanone,Homoisoflavone,Homoisoflavones,Isoflavone,Isoflavone Derivative,3-Benzylchroman-4-Ones,3-Benzylidene-4-Chromanones,Isoflavone Derivatives,3 Benzylchroman 4 One,3 Benzylchroman 4 Ones,3 Benzylidene 4 Chromanone,3 Benzylidene 4 Chromanones,Derivative, Isoflavone,Derivatives, Isoflavone
D010841 Pia Mater The innermost layer of the three meninges covering the brain and spinal cord. It is the fine vascular membrane that lies under the ARACHNOID and the DURA MATER. Mater, Pia,Maters, Pia,Pia Maters
D011464 Epoprostenol A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY). Prostacyclin,Prostaglandin I2,Epoprostanol,Epoprostenol Sodium,Epoprostenol Sodium Salt, (5Z,9alpha,11alpha,13E,15S)-Isomer,Flolan,Prostaglandin I(2),Veletri
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011505 Protein-Tyrosine Kinases Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors. Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D011809 Quinones Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
D006935 Hypercapnia A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000831 Animals, Newborn Refers to animals in the period of time just after birth. Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals
D000959 Antihypertensive Agents Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. Anti-Hypertensive,Anti-Hypertensive Agent,Anti-Hypertensive Drug,Antihypertensive,Antihypertensive Agent,Antihypertensive Drug,Anti-Hypertensive Agents,Anti-Hypertensive Drugs,Anti-Hypertensives,Antihypertensive Drugs,Antihypertensives,Agent, Anti-Hypertensive,Agent, Antihypertensive,Agents, Anti-Hypertensive,Agents, Antihypertensive,Anti Hypertensive,Anti Hypertensive Agent,Anti Hypertensive Agents,Anti Hypertensive Drug,Anti Hypertensive Drugs,Anti Hypertensives,Drug, Anti-Hypertensive,Drug, Antihypertensive,Drugs, Anti-Hypertensive,Drugs, Antihypertensive

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