title: Ergopeptines bromocriptine and ergovaline and the dopamine type-2 receptor inhibitor domperidone inhibit bovine equilibrative nucleoside transporter 1-like activity.
abstract: Neotyphodium coenophialum-infected tall fescue contains ergopeptines. Except for interactions with biogenic amine receptors (e.g., dopamine type-2 receptor, D2R), little is known about how ergopeptines affect animal metabolism. The effect of ergopeptines on bovine nucleoside transporters (NT) was evaluated using Madin-Darby bovine kidney (MDBK) cells. Equilibrative NT1 (ENT1)-like activity accounted for 94% of total NT activity. Inhibitory competition (IC(50)) experiments found that this activity was inhibited by both bromocriptine (a synthetic model ergopeptine and D2R agonist) and ergovaline (a predominant ergopeptine of tall fescue). Kinetic inhibition analysis indicated that bromocriptine inhibited ENT1-like activity through a competitive and noncompetitive mechanism. Domperidone (a D2R antagonist) inhibited ENT1 activity more in the presence than in the absence of bromocriptine and displayed an IC(50) value lower than that of bromocriptine or ergovaline, suggesting that inhibition was not through D2R-mediated events. These novel mechanistic findings imply that cattle consuming endophyte-infected tall fescue have reduced ENT1 activity and, thus, impaired nucleoside metabolism.
authors.affiliation: Department of Animal and Food Sciences, University of Kentucky, Lexington, Kentucky 40546, United States.
authors.forename: Edwena D
authors.initials: ED
authors.lastname: Miles
authors.forename: Yan
authors.initials: Y
authors.lastname: Xue
authors.forename: James R
authors.initials: JR
authors.lastname: Strickland
authors.forename: James A
authors.initials: JA
authors.lastname: Boling
authors.forename: James C
authors.initials: JC
authors.lastname: Matthews
mesh_terms: D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D004294:Domperidone / Q000494:pharmacology*; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D033721:Equilibrative Nucleoside Transporter 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D004879:Ergotamines / Q000494:pharmacology*; D015870:Gene Expression; D007668:Kidney; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D014529:Uridine / Q000378:metabolism; D014662:Vasoconstrictor Agents
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D033721:Equilibrative Nucleoside Transporter 1; D004879:Ergotamines; D011954:Receptors, Dopamine; D014662:Vasoconstrictor Agents; C076760:ergovaline; D001971:Bromocriptine; D004294:Domperidone; D014529:Uridine