Abstract
The term functionomics (Amin 2003, Neumann et al. 2004) refers to a postgenomic integrated Systems Biology (Attur et al. 2002) using a multidimensional approach for cells, tissues and organs. It considers current or future involvement among genomics, proteomics or metabolomics, including the main factors that cause biological responses and modulation under different conditions. Our objective in the present review is to summarize the contemporary understanding of functionomics of smooth muscle pharmacology, based on the results obtained on the pregenomic era during several years in our laboratory. The present approach is based on the knowledge of the dynamics of the receptor system, which comprises a cascade of phenomena, leading from the drug administration to the final biological response. We will describe several conditions in which the final effect is modified, based on perturbations induced on drug absorption, distribution, metabolism, interaction with receptors and mobilization of second messengers, as well as by interactions with a second receptor system. We will also discuss the gaps that need to be fulfilled in order to obtain a clear and better understanding of the receptor system in smooth muscle, and to narrow the bridge between ourknowledge of the function of biological systems, genomics, and other recently introduced areas.
Highlights
Less than 10 years ago, the outstanding journal Science published a number of reviews under the title “Wholeistic Biology” (Chong and Ray 2002)
A number of technical obstacles remain before functionomics can have strengthened its interpretation in conjunction with routine genomics, proteomics and metabolomics: (a) more than 40% of the 35,000 genes have not been ascribed any functional attribute, neither a biochemical or cellular function nor a function at the tissue/organism level (Attur et al 2002); (b) on the other hand, there is a large number of functions that still remain to be correlated with genes and proteins (Amin 2003); (c) when dealing with a gene-driven approach and a phenotype-driven approach, it has to be considered that in general the genetic information is static, while the functional correlate is dynamic (Davidson et al 2002)
We have described that the density of rianodine receptor in sarcosplasmic reticulum is decreased by about 45% after denervation of the vas deferens
Summary
Less than 10 years ago, the outstanding journal Science published a number of reviews under the title “Wholeistic Biology” (Chong and Ray 2002). A major challenge to be foreseen in functionomics is the integration of proteomics with genomics and metabolomics data, and mainly the integration with their physiological and pathophysiological functional interpretation, in conjunction with clinical results and epidemiology To explore such a vast space, new forms to exploit and link these fields with pharmacological data will be essential to ask possibly new kinds of questions about the complex nature of therapeutics. Various alterations have been detected in vas deferens after different types of spontaneous or induced perturbations, such as denervation, castration, transplantation, hypothermia, aging, genetic hypertension, neurodegenerative diseases, or the involvement of a second receptor system These points will be summarized below, in the light of the alleged receptor system cascade, as functional candidates for the 40% of gene population whose function is still unknown
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