Functional antagonism between cAMP and cGMP on permeability of coronary endothelial monolayers.
The role of the intracellular second messengers guanosine 3', 5'-cyclic monophosphate (cGMP) and adenosine 3', 5'-cyclic monophosphate (cAMP) in the control of macromolecule permeability was studied in cultured monolayers of microvascular coronary endothelial cells from rat. Macromolecule permeability was determined as passage of fluorescein isothiocyanate (FITC)-labeled albumin across the monolayers. Activation of adenylyl cyclase by the beta-adrenoceptor agonist isoproterenol (Iso; 10(-5) M) and the A2-adenosine receptor agonist 5'-(N-ethylcarboxamido)-adenosine (NECA; 10(-7) M) induced an increase in cellular cAMP contents that was accompanied by an increase in albumin flux. Effects of Iso and NECA on cellular cAMP level and albumin flux could be antagonized by a stimulator of the particular guanylyl cyclase, atrial natriuretic peptide (ANP; 10(-7) M), and stimulators of the soluble guanylyl cyclase, 3-morpholinosydnonimine (SIN-1; 10(-7) M) and sodium nitroprusside (SNP; 10(-6) M). ANP, SIN-1, and SNP also reduced cAMP content and basal macromolecule flux in unstimulated monolayers. 8-Bromoguanosine 3', 5'-cyclic monophosphate (8-BrcGMP; 5 x 10(-6) M), a stimulator of protein kinase G, reduced the increase in albumin flux under Iso (10(-5) M), NECA (10(-7) M), or 8-bromoadenosine 3', 5'-cyclic monophosphate (8-BrcAMP; 5 x 10(-6) M). The present study shows that cGMP and cAMP are functional antagonists in the control of macro molecule permeability.
Hempel
A
A
Physiologisches Institut, Justus-Liebig-Universität, Giessen, Germany.
Noll
T
T
Muhs
A
A
Piper
H M
HM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology*; D002478:Cells, Cultured; D003326:Coronary Circulation / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000493:pharmacokinetics
D012709:Serum Albumin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium