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.