Catecholamine-induced vasoconstriction is sensitive to carbonic anhydrase I activation.
We studied the relationship between alpha- and beta-adrenergic agonists and the activity of carbonic anhydrase I and II in erythrocyte, clinical and vessel studies. Kinetic studies were performed. Adrenergic agonists increased erythrocyte carbonic anhydrase as follows: adrenaline by 75%, noradrenaline by 68%, isoprenaline by 55%, and orciprenaline by 62%. The kinetic data indicated a non-competitive mechanism of action. In clinical studies carbonic anhydrase I from erythrocytes increased by 87% after noradrenaline administration, by 71% after orciprenaline and by 82% after isoprenaline. The increase in carbonic anhydrase I paralleled the increase in blood pressure. Similar results were obtained in vessel studies on piglet vascular smooth muscle. We believe that adrenergic agonists may have a dual mechanism of action: the first one consists of a catecholamine action on its receptor with the formation of a stimulus-receptor complex. The second mechanism proposed completes the first one. By this second component of the mechanism, the same stimulus directly acts on the carbonic anhydrase I isozyme (that might be functionally coupled with adrenergic receptors), so that its activation ensures an adequate pH for stimulus-receptor coupling for signal transduction into the cell, resulting in vasoconstriction.
Romanian Medical Academy, Center for Research and Medical Assistance, Simleu Silvaniei, Salaj, Romania. ccam@netcompsj.ro
I
I
Puscas
M
M
Coltau
L
L
Gilau
R
R
Pasca
G
G
Domuta
M
M
Baican
A
A
Hecht
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D002256:Carbonic Anhydrases / Q000302:isolation & purification / Q000378:metabolism*; D002395:Catecholamines / Q000494:pharmacology*; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009921:Metaproterenol / Q000494:pharmacology; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D015398:Signal Transduction; D014661:Vasoconstriction / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D007527:Isoenzymes; D009921:Metaproterenol; D002256:Carbonic Anhydrases; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine