GREEN, A.K.*; HALEY, S.L.; KARASOV, W.H.; BARNES, D.M.; DEARING, D.M.; Univ. of Wisconsin, Madison; Univ. of Utah; Univ. of Wisconsin, Madison; Univ. of Wisconsin, Madison; Univ. of Utah: Total capacity of P-glycoprotein higher in the specialist herbivore Neotoma stephensi than the congeneric generalist Neotoma albigula
P-glycoprotein (Pgp) is a membrane-bound, ATP-dependent, transport protein found in both invertebrates and vertebrates. Generally found on the apical side of barrier epithelia in many tissues, Pgp decreases accumulation of many cytotoxic compounds including plant secondary metabolites and pollutants. We hypothesized that a mammalian herbivore that consumes high quantities of plant secondary compounds exhibits higher Pgp activity than a herbivore that avoids these compounds. We tested this hypothesis with the genus Neotoma that includes the juniper specialist, N. stephensi and the allopatric generalist, N. albigula that is unable to maintain body mass on high juniper diet. In both species we measured accumulation of a model Pgp substrate, 3H-digoxin, in everted sections of proximal, mid, and distal small intestine with and without 10 uM cyclosporin A (CsA), a known competitive inhibitor of Pgp. Increased Pgp activity results in a greater difference in digoxin accumulation between CsA and control. We averaged this measure in the three sections and multiplied by total small intestine length, then corrected for total body mass to estimate scaled total capacity. There was a significant difference among species (p=0.02) with the juniper specialist, N. stephensi, exhibiting a 1.8 fold higher capacity than the generalist, N. albigula (p<0.01). These data prevent us from rejecting our hypothesis indicating Pgp may play a role in the ability of N. stephensi to tolerate juniper. Supported by USDA (Hatch) WISO4322 NSF IBN-9723793 IBN-0216709
