Transporting functions

Undesired Effects of Drugs that Interfere with Transporter Function... 

MDMA overdose as well as the concomitant consumption of selective serotonin reuptake inhibitors (SSRI) with other dmgs that exert serotoninergic effects (such as inhibitors of monoamine oxidase) can rapidly lead to the serotonin syndrome. Its symptoms, which are reversible upon cessation, of the drug include confusion, muscle rigidity in the lower limbs, and hyperthermia suggesting an acute reaction to serotonin overflow in the CNS. Blocking the function of SERT outside the brain causes side effects (e.g., nausea), which may be due to elevated 5HT however , impairment of transporter function is not equivalent to direct activation of 5HT recqrtors in causing adverse effects such as fibrosis and pulmonary hypertension. 

Pathogenesis of MH is not completely understood. Skeletal muscle, however, is the one tissue in MH with proven abnormalities, and it is further thought that the basic defect that causes the syndrome lies in the calcium regulation system found within the myoplasm. For example, calcium transport function appears to be decreased in the sarcoplasmic reticulum, mitochondria, and sarcolemma. Thus, the suggestion has been made that MH is characterized by a generalized membrane defeet. 

Chang C, Ray A and Swaan P. In silico strategies for modeling membrane transporter function. Drug Discov Today 2005 10 663-71. 

Na oi and was partially blocked by amiloride but not by cimetidine. Since these investigators also found that amiloride and cimetidine bound competitively with Na" at the external transport site of the placental brush border Na /H exchanger, they concluded that the vicinal dithiol groups are necessary for transport function but are located at a site distinct from the external transport site. 

Figure 25. Formation of an artificial structure of metal nanoparticles by dip pen nanolithography using an AFM (a), tip to transport functionalized thiol molecules onto a gold surface (b) and to trap the nanoparticles (c).

Caeruloplasmin (Cp) is an acute phase glycoprotein with a copper transport function. At least 90% of total plasma copper is bound to Cp with the remaining 10% associated with albumin, histidine and small peptides. Lipid peroxidation requires the presence of trace amounts of transition metals and the copper-containing active site of Cp endows it with antioxidant capacity... 

Figure 10 shows small-time fits to the thermal conductivity using the above functional form. It can be seen that quite good agreement with the simulation data can be obtained with this simple time-dependent transport function. Such a function can be used in the transient regime or to characterize the response to time-varying applied fields. 

Middleton, L.S., Cass, W.A., and Dwoskin, L.P., Nicotinic receptor modulation of dopamine transporter function in rat striatum and medial prefrontal cortex, J. Pharmacol. Exp. Then, 308, 367, 2003. 

Berman, S.B., Zigmond, M.J., Hastings, T.G. Modification of dopamine transporter function effect of reactive oxygen species and dopamine. J. Neurochem. 67 593, 1996. 

Metzger, R.R., Haughey, H.M., Wilkins, D.G. et al. Methamphetamine-induced rapid decrease in dopamine transporter function role of dopamine and hyperthermia. J. Pharmacol. Exp. Ther. 295 1077, 2000. 

Fleckenstein, A.E., Hanson, G.R. Impact of psychostimulants on vesicular monoamine transporter function. Eur. J. Pharmacol. 479 283, 2003. 

Mash D., Pablo J., Ouyang Q., Hearn W., Izenwasser S. Dopamine transport function is elevated in cocaine users. J. Neumchem. 81 292, 2002. 

Since cocaine potentiates dopaminergic neurotransmission by binding to DA transporter and blocking reuptake, persisting increases in DA transporter function after cocaine levels have fallen... 

---