PMID- 1393276
OWN - NLM
STAT- MEDLINE
DCOM- 19921120
LR  - 20190509
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 106
IP  - 4
DP  - 1992 Aug
TI  - Human bronchial cyclic nucleotide phosphodiesterase isoenzymes: biochemical and 
      pharmacological analysis using selective inhibitors.
PG  - 1028-34
AB  - 1 The aims of the present study were to characterize the cyclic nucleotide 
      phosphodiesterase (PDE) isoenzyme activities present in human bronchi and to 
      examine the ability of selective isoenzyme inhibitors to relax histamine and 
      methacholine precontracted preparations of human bronchi. 2 Three separations of 
      pooled human bronchial tissue samples were performed. Ion-exchange chromatography 
      showed that the soluble fraction of human bronchial preparations contains PDE I, 
      II, III, IV and V isoenzyme activities. Multiple forms of PDE I and PDE IV were 
      observed and PDE IV was the main cyclic AMP hydrolytic activity. 3 
      3-Isobutyl-l-methylxanthine (IBMX) non-selectively inhibited all separated 
      isoenzyme activities. Zaprinast selectively inhibited PDE V, but also effectively 
      inhibited one of the two PDE I isoforms identified. The PDE IV selective 
      inhibitors rolipram and RO-201724, inhibited the PDE IV activities as did the 
      dual PDE III/IV inhibitor, Org 30029. Org 9935, a PDE III selective inhibitor, 
      potently attenuated part of the PDE IV activity peak in one of three separations 
      performed, indicating that some PDE III activity may co-elute with PDE IV under 
      the experimental conditions employed. 4 PDE IV-selective (rolipram), PDE 
      III-selective (Org 9935) and dual PDE III/IV (Org 30029) inhibitors were 
      effective relaxants of human bronchial smooth muscle. The PDE V/PDE I inhibitor, 
      zaprinast was relatively ineffective. 5 The present study demonstrates in human 
      bronchi, as in animal airways smooth muscle, that inhibitors of PDE III, PDEIV 
      and dual PDE III/IV have potentially useful bronchodilator activity and are 
      worthy of further consideration as anti-asthma drugs.
FAU - de Boer, J
AU  - de Boer J
AD  - Department of Pharmacology and Therapeutics, A Deusinglaan, Groningen, The 
      Netherlands.
FAU - Philpott, A J
AU  - Philpott AJ
FAU - van Amsterdam, R G
AU  - van Amsterdam RG
FAU - Shahid, M
AU  - Shahid M
FAU - Zaagsma, J
AU  - Zaagsma J
FAU - Nicholson, C D
AU  - Nicholson CD
LA  - eng
PT  - Journal Article
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Isoenzymes)
RN  - EC 3.1.4.17 (3',5'-Cyclic-AMP Phosphodiesterases)
SB  - IM
MH  - 3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors/*metabolism
MH  - Bronchi/*enzymology
MH  - Chemical Fractionation
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - In Vitro Techniques
MH  - Isoenzymes/antagonists & inhibitors/*metabolism
MH  - Muscle Relaxation/drug effects
MH  - Muscle, Smooth/enzymology
PMC - PMC1907637
EDAT- 1992/08/01 00:00
MHDA- 1992/08/01 00:01
PMCR- 1993/08/01
CRDT- 1992/08/01 00:00
PHST- 1992/08/01 00:00 [pubmed]
PHST- 1992/08/01 00:01 [medline]
PHST- 1992/08/01 00:00 [entrez]
PHST- 1993/08/01 00:00 [pmc-release]
AID - 10.1111/j.1476-5381.1992.tb14451.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 1992 Aug;106(4):1028-34. doi: 10.1111/j.1476-5381.1992.tb14451.x.