Developmental regulation of kidney and liver SLC and ABC drug transporters and drug metabolizing enzymes: the role of remote organ communication.

Developmental regulation of kidney and liver SLC and ABC drug transporters and drug metabolizing enzymes: the role of remote organ communication.

Expert Opin Drug Metab Toxicol. 2018 May 10;:

Authors: Momper JD, Nigam SK

Abstract
INTRODUCTION: The ontogeny of drug transport and metabolism is generally studied independently in tissues, yet in the immediate postnatal period the developmental regulation of transporters and metabolizing enzymes must be coordinated. Using the Remote Sensing and Signaling Hypothesis as a framework, we describe how a systems physiology view helps to make sense of how inter-organ communication via hepatic, renal, and intestinal transporters and drug metabolizing (DMEs) enzymes is regulated from the immediate postnatal period through adulthood. Areas covered: This review examines patterns of developmental expression and function of transporters and DMEs with a focus on how cross-talk between these proteins in the intestine, liver, and kidney may be coordinated postnatally to optimize levels of metabolites and endogenous signaling molecules as well as gut-microbiome products. Expert Opinion/Commentary: Developmental expression is considered in terms of the Remote Sensing and Signaling Hypothesis, which addresses how transporters and DMEs participate in inter-organ and inter-organism small molecule communication in health, development, and disease. This hypothesis, for which there is growing support, is particularly relevant to the "birth transition" and post-natal developmental physiology when organs must deal with critical physiological tasks distinct from the fetal period and where remote inter-organ and possibly inter-organismal (e.g. gut microbiome) communication is likely to be critical to maintain homeostasis.

PMID: 29746174 [PubMed - as supplied by publisher]

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