| Reference | 1. Eur J Pharmacol. 2001 Apr 20;418(1-2):111-6.
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SQ22536 and W-7 inhibit forskolin-induced cAMP elevation but not relaxation in
newborn ovine pulmonary veins.
<br>
Gao Y(1), Raj JU.
<br>
Author information: <br>
(1)Department of Pediatrics, Harbor-UCLA Medical Center, University of
California, Los Angeles, School of Medicine, Torrance, CA 90509, USA.
[email protected]
<br>
The role of cAMP in forskolin-induced relaxation was studied in isolated
pulmonary veins of newborn lambs (7-12 days). In vessels preconstricted with
endothelin-1, forskolin at concentrations < or =10(-7) M had no effect on cAMP
content and adenylyl cyclase activity but caused up to 50% relaxation. At higher
concentrations, forskolin markedly elevated cAMP content and adenylyl cyclase
activity and caused a further relaxation. SQ22536
[9-(tetrahydro-2-furanyl)-9H-purin-6-amine; an adenylyl cyclase inhibitor] and
W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide; a calmodulin-dependent
adenylyl cyclase inhibitor] had no significant effect on forskolin-induced
relaxation but markedly inhibited the elevation of cAMP content and adenylyl
cyclase activity caused by forskolin. Rp-8-CPT-cAMPS
[8-(4-chlorophenylthio)-adenosine-3/’,5/’-cyclic monophosphorothioate; an inhibitor
of cAMP-dependent protein kinases] and Rp-8-Br-PET-cGMPS (beta-phenyl-1,
N(2)-etheno-8-bromoguanosine-3/’,5/’-cyclic monophosphorothioate; an inhibitor of
cGMP-dependent protein kinases) attenuated the relaxation caused by a cAMP analog
but not that caused by forskolin. These results suggest that cAMP may not play a
major role in forskolin-induced relaxation of pulmonary veins of newborn lambs.
<br>
2. Br J Pharmacol. 1999 Feb;126(4):845-7.
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Effects of the adenylyl cyclase inhibitor SQ22536 on iloprost-induced
vasorelaxation and cyclic AMP elevation in isolated guinea-pig aorta.
<br>
Turcato S(1), Clapp LH.
<br>
Author information: <br>
(1)Centre for Clinical Pharmacology, Wolfson Institute for Biomedical Research,
Department of Medicine, UCL, London, England, UK.
<br>
The stable prostacyclin analogue, iloprost relaxes a variety of blood vessels and
increases cyclic AMP, although the relationship between adenosine 3/’: 5/’-cyclic
monophosphate (cyclic AMP) and vasorelaxation remains unclear. We therefore
investigated the effect of the adenylyl cyclase inhibitor,
9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536) on iloprost-mediated
relaxation and cyclic AMP elevation in endothelium-denuded aortic strips.
Iloprost (1-1000 nM) caused a concentration-dependent inhibition of phenylephrine
(1-6 microM) contractions, the responses being unaffected by pre-incubation with
SQ22536 (100 microM) for 30 min. In other experiments 60 nM iloprost caused a 64%
inhibition of phenylephrine contractions concomitant with a 3 fold rise in cyclic
AMP. SQ22536 completely abolished the iloprost-induced elevation in cyclic AMP
while having no significant effect on relaxation. Our results therefore strongly
suggest that cyclic AMP-independent pathways are responsible for the vasorelaxant
effects of iloprost in guinea-pig aorta.
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3. Comp Biochem Physiol C. 1991;99(1-2):209-11.
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Actions of vasopressin and isoprenaline on the ionic transport across the
isolated frog skin in the presence and the absence of adenyl cyclase inhibitors
MDL12330A and SQ22536.
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Lippe C(1), Ardizzone C.
<br>
Author information: <br>
(1)Institute of General Physiology, University of Bari, Italy.
<br>
1. The effects of both adenyl cyclase inhibitors (MDL12330A and SQ22536) have
been studied on the ionic transport induced by vasopressin and isoprenaline
across the frog skin. 2. MDL12330A inhibits the vasopressin action on the
short-circuit current (SCC), confirming that this effect is cAMP-mediated. 3. On
the other hand, isoprenaline action on the SCC is unaffected by MDL12330A.
However, this lack of effect is not a sufficient argument against the role of
cAMP in this action; in fact, as MDL12330A is also an inhibitor of cAMP
phosphodiesterase, this action could mask the inhibitory effect of the drug on
adenyl cyclase. 4. By using the other adenyl cyclase inhibitor (SQ22536),
probably deprived of effect on the cAMP phosphodiesterase, we obtained a strong
inhibition of isoprenaline action on the SCC. Thus we conclude that the actions
of isoprenaline on the ionic transport across the frog skin are also
cAMP-mediated.
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