The role of cyclic nucleotides in the action of peripheral-type benzodiazepine receptor ligands in rat aorta.
1. Peripheral-type benzodiazepine ligands (Ro 5-4864, AHN-086, PK 11195 and PK 14105) inhibit, in a concentration-dependent and non-competitive manner, noradrenaline-induced contractions in isolated rat aortic rings (IC50 values: 24 +/- 1.8, 49 +/- 2.5, 15 +/- 1.2, 49 +/- 3.2 microM, respectively). 2. This effect is probably not mediated by peripheral-type benzodiazepine receptors and is not related to the presence of endothelium. 3. All compounds inhibited phosphodiesterase activity in vitro. 4. From the results obtained with nucleotide analogs, calcium antagonists and specific inhibitors of PDE isoenzymes, it can be concluded that the actions of AHN-086 and PK 11195 are related to effects on PDE I, III and IV.
Gimeno
M
M
Laboratory of Pharmacology and Pharmacognosy, Faculty of Pharmacy, University of Barcelona, Spain.
Pallás
M
M
Newman
A H
AH
Camarasa
J
J
Escubedo
E
E
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009712:Nucleotides, Cyclic / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*
D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D008024:Ligands; D009712:Nucleotides, Cyclic; D010726:Phosphodiesterase Inhibitors; D011963:Receptors, GABA-A