Effects of rolipram and siguazodan on the human isolated bronchus and their interaction with isoprenaline and sodium nitroprusside.
1 The effects of the selective inhibitors of cyclic AMP phosphodiesterase type IV (rolipram) and type III (siguazodan) and their interactions with isoprenaline and sodium nitroprusside have been studied in the human isolated bronchus. 2 On bronchi under resting tone rolipram was, in terms of potency (pD2 = 7.77 +/- 0.14, n = 8), very similar to isoprenaline (pD2 = 7.31 +/- 0.12, n = 12) and salbutamol (pD2 = 7.12 +/- 0.17, n = 10) and approximately 10 fold more potent than siguazodan (pD2 = 6.80 +/- 0.12, n = 6). In terms of efficacy (Emax, expressed as percentage of maximal effect induced by theophylline 3 mM), both rolipram and siguazodan were less efficient (Emax = 74 +/- 6.7%, n = 8 and 66 +/- 7.5%, n = 6, respectively) than isoprenaline (Emax = 98 +/- 0.4%, n = 12) and salbutamol (Emax = 83 +/- 2.4%, n = 10). 3 During precontraction induced by methacholine (3 x 10(-7) M) or acetylcholine (10(-3) M), concentration-response curves to rolipram and siguazodan were shifted to the right and maximal effects reduced. Rolipram was more potent than siguazodan and, in terms of efficacy, it was less active. 4. Rolipram 10(-8) and 10(-7) M but not siguazodan potentiated the effects of isoprenaline as shown by the shift to the left of the concentration-response curve to isoprenaline. Sodium nitroprusside-induced relaxation was not modified by either drug. 5. These results show that rolipram is a potent relaxant of the human isolated bronchus, potentiating the effects of beta-adrenoceptor stimulation and suggest that, as previously demonstrated in other species(guinea-pig, cow) (Tomkinson et al., 1993), there may be a connection between the beta2-adrenoceptor subtype, which predominate in human airway smooth muscle, and the cyclic AMP phosphodiesterase type IV.
Qian
Y
Y
Faculté de Médecine Paris-Ouest, France.
Naline
E
E
Karlsson
J A
JA
Raeburn
D
D
Advenier
C
C
D000420:Albuterol / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D020889:Rolipram
D006146:Guanidines; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D011760:Pyrrolidinones; D009599:Nitroprusside; C056215:siguazodan; D020889:Rolipram; D007545:Isoproterenol; D000420:Albuterol