Cellular adaptations

Pharmocodynamic tolerance develops in response to continued application of drugs, by mechanisms that include reversible cellular adaptation processes, such as receptor desensitization, internalization and downregu-lation as well as changes in the activity and levels of other components of the receptor s signal transduction pathways. 

Hormones, cytokines, interleukins, and growth factors use a variety of signaling mechanisms to facilitate cellular adaptive responses. 

Fleming, W. W. Cellular adaptation journey from smooth muscle cells to neurons. J. Pharmacol. Exp. Ther. 291 925-931,1999. 

Another level of cellular adaptation to psychotropic drug exposure involves the change in neuronal number through neurogenesis. Recent research has demonstrated that in the adult hippocampus, new cells constantly arise from immature neural precursor cells in the subgranular zone of the dendate gyrus, migrate into... 

The mechanisms underlying (he development of tolerance are not fully understood. Biochemically, it may he attractive to explain tolerance by decreased absorption, altered distribution, increased biotransfomiatiun, and/or increased excretion of the drug However, these processes have been shown to he unrelated to (he development of tolerance. Thus, cellular adaptation offers the greatest likelihood for clarifying the phenomenon. Evidence for cellular adaptation is the finding that (he respiration of chemically stimulated cortical slices of brain front normal rats is markedly deptessed by morphine, whereas the respiration of those from rats chronically dosed with morphine is unaffected... 

Crowe, J.H., L.M. Crowe, J.E. Carpenter, S. Prestrelski, F.A. Hoekstra, P. Araujo, and A. Panek (1997). Anhydrobiosis cellular adaptation to extreme dehydration. In Handbook of Physiology, Section 13 Comparative Physiology, Yol. II, pp. 1445-1477. ed. W. Danztler. New York Oxford. 

Kumar, V., Abbas, A. K., and Fausto, N. Cellular adaptations, cell injury, and cell death. In Robbins and Cotran Pathologic Basis of Disease, 7th ed. Elsevier Saunders, Philadelphia, 2005, pp. 3 46. 

Aerobic exercise inyolyes endurance training. As the body performs activities for extended periods, physiological and cellular adaptations occur (10-12). These adaptations focus on the ability of the body to supply oxygen to the muscle cells, the capacity of the cells to utilize oxygen, and a shift in the fuel source to greater use of fatty acids. The magnitude of these changes defines aerobic capacity and endurance. 

Subbaiah CC., Sachs MM. Molecular and cellular adaptations of maize to flooding stress. Annals of Botany 2003 91(2) 119-127. 

Studies of cellular adaptation to cannabinoid drugs have identified cellular changes that could predict the mechanism of synaptic plasticity. Homologous desensitization of adenylyl cyclase inhibition was observed within minutes of ex-... 

In the 1980s it was established that there are cellular adaptation mechanisms... 

Occurs with continued use and is functional (pharmacodynamic), with changes in cellular adaptive responses but not receptor numbers. Tolerance can be marked for the CNS actions including analgesia, euphoria, and respiratory depression, but it occurs minimally in terms of miosis and the effects on GI motility. Cross-tolerance occurs between individual opioid analgesics. 

IkB-q (inhibitor of transcription factor NF-kB)), proteins that regulate cellular adaptation to hypoxic stress (i.e., HIF-lct), and proteins related to aberrant gene expression in tumors (e.g., c-Jun, /3-catenin, IttB-a, E2F1). Proteasome inhibitors are under development as new antitumor chemotherapeutic agents and the proteasome inhibitor bortezomib (PS-341, Velcade) has been approved by the U.S. Food and Drug Administration (FDA). 

Complex late adaptations occur upon repeated treatment with SSRIs, including indirect enhancement of NE output by reduction of tonic inhibitory effects of S-HT heteroreceptors. Finally, similar nuclear and cellular adaptations occur as with the tricyclic antidepressants, including increased intraneuronal cyclic AMP, activation/phosphorylation of transcription factors (e.g., CREB), and increased production of BDNF. 

Tolerance to and withdrawal from the opioids is explained by the cellular adaptation that occurs on repeated activation of p opioid receptors (60). When an agonist binds to the p receptor, Gi/o second messenger proteins are activated, and inhibition of adenylate cyclase occurs. Continual activation of the receptors results in an upregulation of adenylate cyclase to compensate for the decrease in cellular concentrations of cAMP. In addition, cellular mechanisms are activated that result in a decrease in the synthesis of Gi/o protein subunits and an internalization of the p... 

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