Beta-adrenergic agonists attenuate fibroblast-mediated contraction of released collagen gels.
The effects of beta-adrenergic agonists on fibroblast-mediated collagen gel contraction were investigated. beta-Agonists isoproterenol and epinephrine significantly attenuated fibroblast-mediated gel contraction in a concentration-dependent manner, whereas alpha-agonist norepinephrine had no effect. The biologically active form of isoproterenol, (-)-isoproterenol, was 10-fold more effective than the optical isoform, (+)-isoproterenol. beta-Antagonists sotalol and propranolol reversed the attenuation caused by 10(-7) M isoproterenol or epinephrine at the concentration of 10(-7) M or 10(-6) M, but the alpha-antagonist phentolamine did not. However, beta1- or beta2-specificity of these effects is not clear. Isobutyl methylxanthine augmented the effect of isoproterenol and also prolonged the duration. Two reagents which are known to increase intracellular adenosine 3',5'-cyclic monophosphate (cAMP), prostaglandin E2 and dibutyryl adenosine 3',5'-cyclic monophosphate, attenuated gel contraction in a concentration-dependent manner. These data suggest that the fibroblast-mediated collagen gel contraction can be modulated by beta-adrenergic agonists and that the effect depends on cAMP.
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Pulmonary and Critical Care Medicine Section, University of Nebraska Medical Center, Omaha 68198-5300, USA.
Adachi
Y
Y
Carnevali
S
S
Romberger
D J
DJ
Spurzem
J R
JR
Rennard
S I
SI
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000187:drug effects* / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D005782:Gels; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D005782:Gels; D003994:Bucladesine; D003094:Collagen; D015232:Dinoprostone; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine