title: P2Y receptors modulate ion channel function through interactions involving the C-terminal domain.
abstract: Nucleotide stimulation of G(q)-coupled P2Y receptors expressed in Xenopus laevis oocytes produces the activation of an endogenous voltage-gated ion channel, previously identified as the transient inward (T(in)) channel. Expression of human P2Y(1), human P2Y(2), rat P2Y(6), human P2Y(11), or skate P2Y receptors in oocytes resulted in modulation of the voltage dependence and inactivation gating of the channel. Expression of the human P2Y(4) receptor, rat M(1)-muscarinic receptor, and human B(1)-bradykinin receptor did not alter the properties of the T(in) channel. Replacement of the C-terminal domain of the human B(1)-bradykinin receptor with the C-terminal domains of either the human P2Y(1) or human P2Y(2) receptor resulted in voltage dependence and inactivation-gating properties, respectively, of the T(in) channel that were similar to those elicited by the respective native P2Y receptor. Systematic truncation of the C-terminal region of the human P2Y(1) receptor identified a short region responsible for modulation of the T(in) channel. This region contains a conserved sequence motif found in all P2Y receptors that modulates the voltage dependence of the T(in) channel. Synthetic 20-mer peptides from the C-terminal domains of human P2Y(1) and P2Y(2) receptors produced a shift in the voltage dependence and slowed inactivation gating, respectively, after injection into oocytes expressing human B(1)-bradykinin or truncated human P2Y(1) receptors. These results indicate that certain P2Y receptors are capable of modulating the voltage sensitivity and inactivation gating of an endogenous oocyte ion channel through interactions involving the C-terminal region of the receptor. Such modulation of ion channel function could also exist in native mammalian cells that express P2Y receptors.
authors.affiliation: Department of Physiology and Molecular Veterinary Biosciences Graduate Program, University of Minnesota, St. Paul, Minnesota 55108, USA.
authors.forename: So Yeong
authors.initials: SY
authors.lastname: Lee
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Wolff
authors.forename: Robert A
authors.initials: RA
authors.lastname: Nicholas
authors.forename: Scott M
authors.initials: SM
authors.lastname: O'Grady
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D004553:Electric Conductivity; D004594:Electrophysiology; D007473:Ion Channels / Q000502:physiology*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000737:chemistry / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D017386:Sequence Homology, Amino Acid; D014982:Xenopus laevis
chemical_list: D007473:Ion Channels; C546382:P2RY1 protein, human; C546385:P2RY2 protein, human; C546384:P2ry1 protein, rat; C546387:P2ry2 protein, rat; D010455:Peptides; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; C099845:purinoceptor P2Y6; D001920:Bradykinin