Comparative effects of vinpocetine and 8-Br-cyclic GMP on the contraction and 45Ca-fluxes in the rabbit aorta.
Vinpocetine is a highly specific inhibitor of calmodulin-dependent phosphodiesterase (CaM-PDE) with an IC50 of 19 microM and produces a significant accumulation of cyclic GMP but not cyclic AMP in rabbit aorta. In isolated rabbit aortic strips, vinpocetine (0.01 and 0.1 mM) inhibited the contraction and 45Ca uptake due to both phenylephrine (1 microM) and KCl (40 mM), whereas 8-Br-cyclic GMP (0.1-1mM) selectively impaired phenylephrine-induced responses. Furthermore, the KCl-stimulated 45Ca efflux in normal Ca2+ buffer, which reflects elevated cytosolic Ca2+, was greatly diminished by vinpocetine but not by 8-Br-cyclic GMP. However, phenylephrine-induced 45Ca efflux and contraction in Ca2+-free buffer, which reflect Ca2+ release from intracellular sites, were similarly inhibited by both vinpocetine and 8-Br-cyclic GMP. The results suggest that vinpocetine may effect vasodilatation through blockade of the slow channel and selective inhibition of CaM-PDE in the vascular smooth muscle.
Chiu
P J
PJ
Department of Pharmacology, Schering-Plough Corporation, Bloomfield, NJ 07003.
Tetzloff
G
G
Ahn
H S
HS
Sybertz
E J
EJ
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001013:Aorta, Thoracic; D002021:Buffers; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D007473:Ion Channels / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D011817:Rabbits; D013552:Swine; D014748:Vinca Alkaloids / Q000494:pharmacology*
D002021:Buffers; D002132:Calcium Radioisotopes; D007473:Ion Channels; D014748:Vinca Alkaloids; C016276:8-bromocyclic GMP; C013983:vinpocetine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D006152:Cyclic GMP; D002118:Calcium