![]() The above results are not consistent with the previously suggested roles for cyclic GMP and cyclic AMP as mediators of smooth muscle contraction and relaxation, respectively. (1978), may result in a net dephosphorylation of the myosin light chains and a concomittant inhibition of the contractile response. Cyclic GMP levels in the depolarized muscles were not significantly changed by isoproterenol or papaverine but were increased approximately 80% by nitroglycerin. The c-AMP effect may be mediated through activation of cyclic AMP-dependent kinase, producing phosphorylation of the myosin light chain kinase which, according to adelstein et al. It was concluded that changes in total tissue levels of cyclic AMP were not responsible for the uterine relaxation caused by nitroglycerin, papaverine or isoproterenol in these experiments. For example, the 40% elevation of cyclic AMP seen 10 min after KCl-depolarization did not cause the muscles to relax, whereas 5 X 10(-9) M isoproterenol caused relaxation with an increase in cyclic AMP levels of only 16% over depolarized controls. However, the magnitudes of the cyclic AMP increases seen after the lower concentrations of isoproterenol were small relative to the increases observed during KCl-contracture alone. Isoproterenol, in concentrations from 5 X 10(-9) M to 10(-6) M, relaxed the depolarized muscles and significantly increased tissue levels of cyclic AMP. At this point both nitroglycerin (4 X 10(-4) M) and papaverine (2 X 10(-5) M) were capable of relaxing the depolarized muscles without significantly increasing cyclic AMP levels. While the mechanism by which exogenous cAMP and specific analogs induce relaxation in some smooth muscle preparations remains unclear, it can be suggested that PKA activation is not necessarily required for the final functional effect.Ten minutes after KCl-depolarization of rat myometrial strips, at which time the muscles were in a state of sustained contracture, tissue levels of adenosine 3',5'-cyclic monophosphate (cyclic AMP) were increased by approximately 40% over relaxed controls, and levels of guanosine 3',5'-cyclic monophosphate (cyclic GMP) were decreased by 40%. This does not support the hypothesis that the kinase is responsible for cAMP-induced relaxation of vascular and non-vascular smooth muscle. The results of the tension and kinase studies demonstrate a lack of correlation between activation of PKA and inhibition of rat vas deferens contraction or relaxation of bovine coronary artery. These controls allowed for a valid assessment of PKA activity in the cyclic nucleotide-treated tissues. As a further precaution, extracellularly associated cAMP and analogs were also washed from bovine coronary artery strips after the incubation period. ![]() 8Br-cAMP (10 - 100 μM) did not affect the coronary artery tension but did activate soluble PKA.īoth smooth muscle preparations were homogenized with charcoal prior to the determination of PKA activity in order to minimize artifactual assay results. dBu-cAMP (10 - 100 μM) affected neither tension nor soluble PKA activity. In the bovine coronary artery, cAMP (10 - 100 μM) relaxed potassium-depolarized helical strips and significantly activated soluble PKA in a dose-dependent manner. The time course of activation of soluble PKA activation by 8Br-cAMP (10 μM) demonstrated that the kinase was significantly activated only after 30 minutes of exposure to the analog. In contrast, 8-bromo-cAMP (8Br-cAMP) (10 -100 μM) did not have any significant effect on inhibition of PE-induced tension after 30 minutes of incubation but, at a concentration of 10 μM, significantly activated both the soluble and particulate fractions of PKA. Overall, DeWalts cordless circular saw is a powerful, smooth-cutting tool. This analog (10 μM) also activated the soluble fraction of PKA but did not activate the particulate fraction kinase. For corded circular saws, you also need a heavy-duty, 15-amp extension cord. Muscarinic receptors expressed on smooth muscle cells are. This hypothesis was tested in two intact smooth muscle preparations, the rat vas deferens and the bovine coronary artery, using exogenously applied cAMP and cAMP analogs.Īfter 30 minutes of incubation, N⁶,2'-0-dibutyryl-cAMP (dBu-cAMP) (1 - 100 μM) inhibited phenylephrine (PE)-induced tension generation in the rat vas deferens in a dose-dependent manner. Inhibition of cyclic AMP accumulation by oxotremorine-M was unaffected by tetrodotoxin and was completely reversed by atropine. It is generally held that adenosine 3',5'-cyclic monophosphate (cAMP) mediates smooth muscle relaxation by the activation of cAMP-dependent protein kinase (PKA). ![]()
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