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PMID: 183155 Published · ppublish English Journal Article

Differentiation of intestinal smooth muscle relaxation caused by drugs that inhibit phosphodiesterase.

Naunyn-Schmiedeberg's archives of pharmacology ·Vol. 293 ·No. 3 ·1976-06-00 ·Pages 257-68

Pöch G, Umfahrer W

Abstract

In this study a number of chemically unrelated smooth muscle relaxants were tested: a) for potency of phosphodiesterase (PDE)-inhibition, using guinea pig colon-PDE and rat erythrocyte-PDE, b) for potency and duration of relaxation of the isolated guinea-pig colon, c) for their interaction with NH4Cl and orciprenaline as well as with "high calcium". Compared with the spasmolytic effect inhibition of guinea pig colon-PDE or rat erythrocyte-PDE was strong for papaverine and some other relaxants but was low or virtually absent with verapamil, hexobendine and bencyclane. The spasmolytic effect of some PDE-inhibitors was found diminished by the PDE-activator NH4Cl. Most of these drugs enhanced the relaxant effect of the "cyclase activator" orciprenaline; the latter are designated A-type drugs. Verapamil, bencyclane, hexobendine and M 13 did not show this type of interaction with NH4Cl and orciprenaline; they are designated B-type drugs. With A-type drugs--but not with B-type drugs--a highly significant correlation was observed between potency of relaxation and inhibition of colon-PDE (r = 0.85) as well as rat erythrocyte-PDE (r = 0.77). The spasmolytic action of aminophylline and papaverine (A-type drugs) was not inhibited by elevation of extracellular calcium to 9 mM, whereas relaxation induced by verapamil and hexobendine (B-type drugs) at 1.8 mM calcium was found abolished by 9 mM calcium. It is concluded that A-type drugs relax guinea-pig colon by inhibition of PDE and accumulation of cAMP, and that B-type drugs in all probability act by (a) cAMP-independent mechanism(s).

MeSH Terms
3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors Aminophylline/pharmacology Ammonium Chloride/pharmacology Animals Calcium/metabolism Carbachol/pharmacology Colon/drug effects Guinea Pigs Hexobendine/pharmacology Isoquinolines/pharmacology Metaproterenol/pharmacology Muscle Contraction/drug effects Muscle, Smooth/drug effects,enzymology Papaverine/pharmacology Parasympatholytics/pharmacology Phosphodiesterase Inhibitors Verapamil/pharmacology
Chemicals
Isoquinolines Parasympatholytics Phosphodiesterase Inhibitors Ammonium Chloride Aminophylline Metaproterenol Carbachol Hexobendine Verapamil Papaverine 3',5'-Cyclic-AMP Phosphodiesterases Calcium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Pöch G
Umfahrer W
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Article Info
Journal
Naunyn-Schmiedeberg's archives of pharmacology
Abbr.
Naunyn Schmiedebergs Arch Pharmacol
ISSN
0028-1298
DOI
10.1007/BF00507348
Published
1976-06-00
Pages
257-68
Language
English
Region
Germany
NLM ID
0326264
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00507348 View journal details
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