cAMP production by piglet cerebral vascular smooth muscle cells: pH(o), pH(i), and permissive action of PGI(2).
In newborn pig pial arterioles and cocultures of cerebral microvascular endothelial and smooth muscle cells, hypercapnia increases cAMP. In the intact cerebral circulation, both the increase in cAMP and the accompanying vasodilation require the presence of PGI(2). Using piglet cerebral microvascular smooth muscle in primary culture, we addressed the hypothesis that, in the presence of PGI(2), hypercapnia-induced changes in extracellular pH cause increases in cAMP. The stable PGI(2)-receptor agonist iloprost did increase production of cAMP in response to combined extracellular pH and pH(i) (11 +/- 6 vs. 32 +/- 10% in the absence and presence of 10(-10) M iloprost, respectively). However, there was no positive dose-response relationship between iloprost concentration and stimulation of cAMP production by acidosis (e.g., 58 +/- 9 vs. 41 +/- 5% in the presence of 10(-12) and 10(-9) M iloprost, respectively). Rapid decreases in pH(i) stimulate the cAMP production. Decreases in extracellular pH do not appear to contribute further. The G protein inhibitor pertussis toxin did not augment cAMP production in response to decreasing pH(i). We conclude that PGI(2) receptor activation permits another mechanism to enhance cAMP generation in response to intracellular, but not extracellular, acidosis and that the mechanism of the permissive effect of PGI(2) does not involve inhibition of a pertussis toxin-sensitive G protein.
Leffler
C W
CW
Laboratory for Research in Neonatal Physiology, Department of Physiology, The University of Tennessee, Memphis, Tennessee 38163, USA. cleffler@physio1.utmem.edu
Balabanova
L
L
Williams
K K
KK
D000138:Acidosis / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003470:Culture Media / Q000737:chemistry; D000242:Cyclic AMP / Q000096:biosynthesis*; D004357:Drug Synergism; D011464:Epoprostenol / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D006863:Hydrogen-Ion Concentration; D016285:Iloprost / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D037342:Pertussis Toxin; D011422:Propionates / Q000494:pharmacology; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000819:agonists; D013552:Swine; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D003470:Culture Media; D011422:Propionates; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D010566:Virulence Factors, Bordetella; D011464:Epoprostenol; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D016285:Iloprost; C029658:propionic acid