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Effects of rolipram and siguazodan on the human isolated bronchus and their interaction with isoprenaline and sodium nitroprusside
Author(s) -
Qian Y.,
Naline E.,
Karlsson J.A.,
Raeburn D.,
Advenier C.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13641.x
Subject(s) - rolipram , isoprenaline , sodium nitroprusside , chemistry , endocrinology , phosphodiesterase inhibitor , medicine , phosphodiesterase , pharmacology , salbutamol , stimulation , asthma , biochemistry , enzyme , nitric oxide
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 (pD 2 = 7.77 ± 0.14, n = 8), very similar to isoprenaline (pD 2 = 7.31 ± 0.12, n = 12) and salbutamol (pD 2 = 7.12 ± 0.17, n = 10) and approximately 10 fold more potent than siguazodan (pD 2 = 6.80 ± 0.12, n = 6). In terms of efficacy (E max , expressed as percentage of maximal effect induced by theophylline 3 m m ), both rolipram and siguazodan were less efficient (E max = 74 ± 6.7%, n = 8 and 66 ± 7.5%, n = 6, respectively) than isoprenaline (E max = 98 ± 0.4%, n = 12) and salbutamol (E max = 83 ± 2.4%, n = 10). 3 During precontraction induced by methacholine (3 × 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 β‐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 β 2 ‐adrenoceptor subtype, which predominate in human airway smooth muscle, and the cyclic AMP phosphodiesterase type IV.