title: P2Y1 receptors expressed by C1 neurons determine peripheral chemoreceptor modulation of breathing, sympathetic activity, and blood pressure.
abstract: Catecholaminergic C1 cells of the rostral ventrolateral medulla (RVLM) are key determinants of the sympathoexcitatory response to peripheral chemoreceptor activation. Overactivation of this reflex is thought to contribute to increased sympathetic activity and hypertension; however, molecular mechanisms linking peripheral chemoreceptor drive to hypertension remain poorly understood. We have recently determined that activation of P2Y1 receptors in the RVLM mimicked effects of peripheral chemoreceptor activation. Therefore, we hypothesize that P2Y1 receptors regulate peripheral chemoreceptor drive in this region. Here, we determine whether P2Y1 receptors are expressed by C1 neurons in the RVLM and contribute to peripheral chemoreceptor control of breathing, sympathetic activity, and blood pressure. We found that injection of a specific P2Y1 receptor agonist (MRS2365) into the RVLM of anesthetized adult rats increased phrenic nerve activity (≈55%), sympathetic nerve activity (38 ± 6%), and blood pressure (23 ± 1 mm Hg), whereas application of a specific P2Y1 receptor antagonist (MRS2179) decreased peripheral chemoreceptor-mediated activation of phrenic nerve activity, sympathetic nerve activity, and blood pressure. To establish that P2Y1 receptors are expressed by C1 cells, we determine in the brain slice preparation using cell-attached recording techniques that cells responsive to MRS2365 are immunoreactive for tyrosine hydroxylase (a marker of C1 cells), and we determine in vivo that C1-lesioned animals do not respond to RVLM injection of MRS2365. These data identify P2Y1 receptors as key determinants of peripheral chemoreceptor regulation of breathing, sympathetic nerve activity, and blood pressure.
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269-3156, USA.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Wenker
authors.forename: Cleyton R
authors.initials: CR
authors.lastname: Sobrinho
authors.forename: Ana C
authors.initials: AC
authors.lastname: Takakura
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Mulkey
authors.forename: Thiago S
authors.initials: TS
authors.lastname: Moreira
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D059331:Adrenergic Neurons / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002628:Chemoreceptor Cells / Q000502:physiology*; D008526:Medulla Oblongata / Q000502:physiology*; D010791:Phrenic Nerve / Q000502:physiology; D051381:Rats; D058472:Receptors, Purinergic P2Y1 / Q000032:analysis / Q000502:physiology*; D012119:Respiration; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: C511689:(N)-methanocarba-2MeSADP; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D058472:Receptors, Purinergic P2Y1; D000244:Adenosine Diphosphate
keywords: hypertension; medulla oblongata; purinergic effects; sleep apnea, obstructive