The sarcoplasmic reticulum in disease and smooth muscle dysfunction: therapeutic potential.
The functions of the sarcoplasmic reticulum (SR) in diseased smooth muscle can be investigated by measuring Ca2+ transients in response to agonist application, and through cell homogenization, isolation of microsomes and measurements of Ca-ATPase activity (SERCA). Such measurements have indicated that contractile dysfunction may be associated with degradation of SERCA in some systems, such as hypertrophied bladder smooth muscle. However, the postulated roles of the SR in smooth muscle function vary from one tissue to another and SR may mediate relaxation as well as contraction. Function seems to depend on the precise location of the SR with respect to the plasma membrane and its Ca2+-activated ion channels, the Ca2+ transporters, the cavaeoli, the mitochondria, and the contractile machinery. In diseases characterized by smooth muscle dysfunction, the size of the smooth muscle cells is frequently altered, as occurs in the hypertrophy seen in gut and bladder obstruction and hypertension. This will inevitably lead to alterations in the morphology and the function of the SR. Any therapeutic potential awaits considerable advances in our understanding of the systems in individual smooth muscles and the development of selective drugs.
Brading
A F
AF
University Department of Pharmacology, Oxford, UK.
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology; D004194:Disease; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008322:Mammals; D009130:Muscle, Smooth / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology; D000099211:Phospholamban
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D000099211:Phospholamban; C506926:ITPR1 protein, human