The fundamental myocellular uptake and retention mechanisms of hexakis (2-methoxyisobutyl Despite this initial success of Tc-MIBI as a flow tracer, controversy exists from in vivo and in vitro experience over whether Tc-MIBI is a pure flow tracer by virtue of its lipophilicity or whether altered metabolic states of myocardium may influence Tc-MIBI kinetics and net accumulation. For example, prolonged metabolic blockade in cultured heart cells significantly reduces myocellular unidirectional uptake of Tc-MIBI.6 In buffer-perfused rabbit heart,7 ouabain alters cellular retention of Tc-MIBI, whereas preliminary data with hypoxia at slow flow rates has also been shown to inhibit Tc-MIBI transcapillary exchange in blood-perfused rabbit heart.8 In an open-chest dog model, Tc-MIBI significantly underestimated reperfusion flow to necrotic and perinecrotic regions compared with microsphere analysis that suggested that Tc-MIBI net uptake reflected myocardial viability.9 In addition, image disparity between 20Ifl and Tc-MIBI has been reported clinically after lytic therapy.10 Conversely, Tc-MIBI overestimated reperfusion flow to ischemic zones in another open-chest dog model.1' These observations are difficult to reconcile because the fundamental mechanisms of extraction, retention, and washout of Tc-MIBI at the vascular and myocellular levels are not established.A significant clue to the cellular mechanisms of uptake and retention of Tc-MIBI may be related to its lipophilic cationic nature. This raises the possibility that Tc-MIBI may be distributed across biological membranes in response to transmembrane potential in a manner similar to other well-characterized lipophilic cations such as tetraphenylphosphonium, rhodamine-123, or the cyanine dyes.'2-'7 Such compounds are sufficiently lipophilic (hydrophobic) to partition into biological membranes but also contain a delocalized charge distributed throughout the molecule, thereby allowing passive distribution of the compound across a bilayer in proportion to an imposed transmembrane electrical potential.12 Because normal myocardial cells maintain a negative plasma membrane potential (Em) that concentrates cations within the cytosol relative to the external buffer and because they also contain a substantial number of mitochondria that generate a large negative potential (Aqi=-150 to -200 mV14) across the inner mitochondrial membrane that will further concentrate cations relative to the cytosol, both potentials would contribute a large driving force for the sequestration of Tc-MIBI within the mitochondrial inner matrix. Therefore, the ratio of Tc-MIBI Previous studies with cultured chick myocardial cells have shown a strong inhibitory effect of prolonged metabolic blockade on Tc-MIBI uptake,6 but the approach did not resolve the fundamental myocellular uptake mechanism. However, preliminary studies in nonmyocardial preparations suggested a potentialdependent uptake mechanism for the agent.18,19 Fully characterizing accumulation in a heart preparation, this report presen...

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S]GTP␥S binding in the olfactory bulb, glia limitans, and cortical subventricular zone of 1-day-old rats, whereas enhanced labeling was not observed in the latter area of 5-day-old rats. Sphingosine 1-phosphate stimulated binding in the cortical and striatal subventricular zones and olfactory bulb in 1-and 5-day-old rats. In the absence of radioligand for sphingosine 1-phosphate and lysophosphatidic acid receptors, [ 35 S]GTP␥S autoradiography provides a unique opportunity to study the spatial distribution, ontogeny, and coupling properties of these receptors.