Key result
Vasoactive agents differentially alter microsomal Ca++ uptake and binding, whereas D-600 has no effect.
Why the study?
The effects of Sr++, aminoglycoside antibiotics, and other agents on Ca++ incorporation by canine aortic microsomes at different Ca++ affinity states were examined to understand their impact on smooth muscle contractility.
Agents affecting smooth muscle contractility alter binding or uptake of Ca++ in differing ways in canine aortic microsomes, highlighting distinct mechanistic pathways for calcium regulation.
Sr++ inhibition of high-affinity Ca++ uptake in canine microsomes is hypothesis-generating; leaves open relevance to human vascular calcium regulation.
The effects of Sr++, aminoglycoside antibiotics and other agents on Ca++ incorporation by canine aortic microsomes have been examined in 0.03 mM Ca++ (high affinity Ca++ components predominate) and in 3.0 mM Ca++ (low affinity Ca++ components predominate) in the presence of 45Ca uptake) and absence (45Ca binding) of ATP. Sr++ inhibited high affinity Ca++ uptake more than binding of Ca++ and reduced low affinity Ca++ uptake and binding only at higher concentrations (3.0-5.0 mM). Similar results were obtained with Sr++ in canine aortic media intimal strips. Neomycin (0.4-1.4 mM) or gentamicin (0.6-2.0 mM) had no significant effect on high affinity Ca++ uptake, but reduced high affinity Ca++ binding and inhibited low affinity Ca++ uptake and binding. Nitroprusside inhibited only high affinity Ca++ uptake and D-600 was without effect. Thus, measurement of Ca++ uptake and binding in smooth muscle microsomal membrane preparations demonstrates that agents affecting smooth muscle contractility can alter binding or uptake of Ca++ in differing ways or, in some cases (e.g. D-600), exert their action by blocking other Ca++-related effects.
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Kutsky et al. (2008) studied this question. Sr++, aminoglycoside antibiotics, nitroprusside, and D-600 was evaluated on Ca++ uptake and binding. Sr++, aminoglycoside antibiotics, and nitroprusside altered high and low affinity Ca++ uptake and binding in canine aortic microsomes in differing ways, while D-600 had no effect.
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