Effect of Rp diastereoisomer of adenosine 3',5' cyclic-monophosphothioate on the cAMP-dependent relaxation of smooth muscle.
The effect of Rp diastereoisomer of adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS) on relaxation elicited by histamine (1-100 microM), forskolin (1-60 microM), papaverine (1-100 microM), vinpocetine (1-100 microM), rolipram (0.1-1 mM), Sp-cAMPS (10-300 microM), 8-BrcAMP (10 microM - 1 mM) and 8-BrcGMP (3 microM - 1 mM) of the previous vanadate-induced contraction was assayed. The effect of Rp-cAMPS on the relaxing effect produced by forskolin, papaverine, vinpocetine, rolipram, Sp-cAMPS and 8-BrcAMP in KCl-induced tonic contraction was also assayed. Histamine, forskolin, papaverine, rolipram, Sp-cAMPS, 8-BrcAMP and 8-BrcGMP, but not vinpocetine, relaxed the vanadate-induced contractions in rat uterus incubated in medium lacking calcium plus EDTA in a concentration-dependent way. Rp-cAMPS (1-300 microM) had no effect on vanadate contraction. However, it antagonized the relaxation elicited by histamine and papaverine, but not that of forskolin, rolipram, Sp-cAMPS, 8-BrcAMP and 8-BrcGMP. Forskolin, papaverine, vinpocetine, rolipram and 8-BrcAMP, but not Sp-cAMPS, relaxed the KCl-induced contraction. Rp-cAMPS antagonized the relaxation elicited by forskolin, papaverine and vinpocetine, but not that of rolipram and 8-BrcAMP. Our results suggest that: a) Rp-cAMPS is an effective PKA inhibitor that could be used to study the involvement of cAMP on drug-induced response in smooth muscle, and b) the effects of Sp-cAMPS, 8-BrcAMP and rolipram were independent of the activation of protein kinases.
Perez-Vallina
J R
JR
Laboratorio de Farmacología, Dpto. Medicina, Facultad de Medicina, Oviedo, Spain.
Revuelta
M P
MP
Cantabrana
B
B
Hidalgo
A
A
D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006632:Histamine / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D010208:Papaverine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram; D013237:Stereoisomerism; D013873:Thionucleotides / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology; D014599:Uterus / Q000187:drug effects* / Q000502:physiology; D014638:Vanadates / Q000494:pharmacology; D014748:Vinca Alkaloids / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D013873:Thionucleotides; D014748:Vinca Alkaloids; D005576:Colforsin; C016957:adenosine-3',5'-cyclic phosphorothioate; D014638:Vanadates; C013983:vinpocetine; D011189:Potassium Chloride; D006632:Histamine; D010208:Papaverine; D000242:Cyclic AMP; D020889:Rolipram