The effects of caffeine on the noradrenaline-sensitive calcium store in rabbit aorta.
The effects of caffeine on the noradrenaline-sensitive Ca store in rabbit aorta have been studied measuring tension development and stimulated 45Ca efflux in Ca-free solution. In addition, the inhibitory effects of caffeine on transmembrane Ca movements and on intracellular Ca release have been investigated, again comparing contractile force and 45Ca fluxes. The maximally effective caffeine concentration fully depletes the noradrenaline-sensitive Ca store as found from both contraction and 45Ca efflux experiments. Within the concentration ranges used in this study for either caffeine and noradrenaline, a linear relation exists between the amplitude of contraction and the amount of stimulated 45Ca efflux. The Ca content of the store (presumably sarcoplasmic reticulum, s.r.) is 74 mumol/kg aorta, corresponding to an s.r. Ca concentration of 5.3 mM. After exposure of the cells to a high-K solution the s.r. Ca concentration reached a value of 8.5 mM. At 37 degrees C the Ca is lost from the store in Ca-free solution with a half-time of 34 min. Although a comparable amount of 45Ca is released by the maximal doses of caffeine and noradrenaline, the caffeine-induced contraction is much smaller than the noradrenaline-induced one. The increase in adenosine 3',5'-cyclic monophosphate (cyclic AMP) after caffeine was less than after noradrenaline, so could not account for the small size of the caffeine-induced contraction. Asynchrony in response to caffeine by successive layers of smooth muscle, and a separate inhibitory action of caffeine, may contribute to the small size of caffeine-induced contractions in thick muscle preparations. Caffeine inhibits high-K-induced contractions by inhibition of Ca influx. Caffeine also inhibits the noradrenaline-induced contractions in Ca-free solution. These inhibitory actions could be dissociated from caffeine-induced release of intracellular Ca.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D011817:Rabbits
D002110:Caffeine; D000242:Cyclic AMP; D002118:Calcium; D009638:Norepinephrine