The emerging role of pharmacology in understanding consumer–prey interactions in marine and freshwater systems

Abstract

Within our lakes, streams, estuaries, and oceans, there is an astounding chemodiversity of secondary metabolites produced by microbes, algae, and invertebrates. Nearly 30 years of study have yielded hundreds of examples in which secondary metabolites alter the foraging behavior or fitness of aquatic consumers, or both. However, our understanding of the mechanisms that mediate the fate and consequences of these metabolites in aquatic consumers remains in its infancy. Interactions between metabolites and consumers at the molecular and biochemical level are the purview of modern pharmacology, which is rooted in the long history of human-drug interactions and can be adopted for ecological studies. Here, we argue that a pharmacological approach to consumer-prey interactions will be as productive within aquatic systems as it has been for understanding terrestrial systems. We review the diversity of secondary metabolites in aquatic organisms, their known effects on the feeding behaviors and performance of aquatic consumers, and the few studies that have attempted to describe their biochemical manipulation within consumer tissues, i.e., their absorption, distribution, metabolism (including detoxification), and excretion. We then highlight vexing issues in the ecology and evolution of aquatic consumer-prey interactions that would benefit from a pharmacological approach, including specialist-versus-generalist feeding strategies, dietary mixing, nutrient-toxin interactions, and taste. Finally, we argue that a pharmacological approach could help to predict how consumer-prey interactions are altered by global changes in pH, water temperature and ultraviolet radiation, or by pollution. Arguably, the state of knowledge of aquatic consumer-prey interactions is equivalent to that faced by ecologists studying terrestrial herbivores in the 1970s; the literature documents profound variation among consumers in their feeding tolerances for secondary metabolites without a thorough understanding of the mechanisms that underlie that variation. The subsequent advancement in our understanding of terrestrial herbivores in the intervening decades provides confidence that applying a pharmacological approach to aquatic consumers will prove equally productive.

A Pharm-Ecological Perspective of Terrestrial and Aquatic Plant-Herbivore Interactions

“…Although the general concepts of pharmacology were introduced to ecologists to explain plant-herbivore interactions 38 years ago (Freeland and Janzen, 1974), the empirical use of pharmacology to understand mechanisms driving foraging patterns in any system is limited (Haley et al, 2008;Magnanou et al, 2009;Marsh et al, 2006b;McLean and Duncan, 2006;Sotka et al, 2009). In contrast to the broad knowledge base that exists on the mechanisms required to process nutrients as well as mechanisms used by domestic and laboratory species to metabolize drugs, there is a general lack of understanding of how PSMs are processed by herbivores, especially in the context of a variable nutrient environment (Appel, 1993;Casarett et al, 2008;Gross and Bakker, 2012;Karasov and Hume, 1997).…”

“…As highlighted above, pharmacological approaches allow The general outcome of the pharm-ecological mechanisms described, to minimize deficits and excesses to maintain homeostasis, is conserved across species for a range of chemicals and therefore can be applied to a variety of systems (see Behmer, 2009;Sotka et al, 2009). Of the parameters outlined in Figure 1, dose (e.g., total intake), metabolism, excretion and foraging response have received the most attention by ecologists (Haley et al, 2008;McLean and Duncan, 2006;.…”

“…The concentration-time profile of a substrate in compartments can be modified by herbivores through mechanical and biochemical mechanisms that influence the absorption, distribution, metabolism, and excretion of substrates. These factors are collectively referred to in pharmacological literature as "ADME" and apply to both terrestrial and aquatic systems (Sotka et al, 2009). Pharmacokinetic studies that determine the concentration-time course may be more informative with respect to predictions of food intake than in vitro kinetic approaches that quantify enzyme activities.…”

“…In invertebrates, fat bodies and the digestive system, including the different gut compartments and the digestive gland, are responsible for the biotransformation of toxins (Appel, 1993;Gross et al, 2008;Hyne and Maher, 2003;Keeley, 1985;Rewitz et al, 2006). The enzymes responsible for the metabolism of drugs have been extensively investigated in laboratory and domestic mammals but far less so with respect to PSMs in wild herbivores, particularly aquatic ones (Dearing et al, 2005;Sotka et al, 2009). Drug metabolizing enzymes are extremely diverse and categorized broadly by function into Phase 1 enzymes such as the cytochromes P450 or Phase 2 enzymes such as glutathione S-transferases and glucuronyltransferases (Casarett et al, 2008).…”

“…Although both nutrients and secondary metabolites influence foraging behavior, there is a general lack of ability to a priori predict diet selection even when the nutritional and chemical profiles of available plants are well documented (Clements et al, 2009;Cruz-Rivera and Hay, 2003;Kool, 1992;Sotka et al, 2009;Yeager et al, 1997).…”