Adrb1 (rat, P18090) - manual literature synthesis

No deep-research provider was available for this review; this file was assembled by hand from
cached publications in publications/ and the UniProt record Adrb1-uniprot.txt. Every claim
carries a provenance tag.

Identity and family

• Rat beta-1 adrenergic receptor, 466 aa, class A (rhodopsin-like) GPCR; UniProt P18090, RGD:2059,
  GeneID 24925. [UniProtKB:P18090 "Belongs to the G protein-coupled receptor 1 family. Adrenergic
  receptor subfamily. ADRB1 sub-subfamily."]
• Cloned from a rat genomic library; single-copy gene, one N-glycosylation site (Asn15) and three
  PKA consensus sites (Ser296, Ser301, Ser401); mRNA highest in pineal gland, moderate in other brain
  regions and heart. PMID:1695899
• Seven helical TM segments (58-81, 96-121, 129-154, 177-199, 222-245, 313-338, 347-366), long
  cytoplasmic C-tail ending in an E-S-K-V class I PDZ ligand. [UniProtKB:P18090 FT TRANSMEM / MOTIF]

Molecular function: Gs-coupled beta1-adrenergic receptor

• Expressed rat receptor binds iodocyanopindolol with KD 24 pM and stimulates adenylyl cyclase with
  potency isoproterenol > norepinephrine = epinephrine (beta1 profile). PMID:1695899
• Native rat beta1-AR is coupled positively to adenylyl cyclase in anterior pituitary and shows
  constitutive activity (inverse agonism of CGP 20712A). PMID:18202135
• Mouse knockout: loss of beta1-AR abolishes isoproterenol-stimulated chronotropy and inotropy and
  sharply reduces cardiac adenylyl cyclase stimulation. PMID:8693001
• Partial agonist clenbuterol binds rat beta1 with KD 38 nM. PMID:6289140

PDZ-ligand interactions, Ras activation and trafficking

• The C-terminal PDZ ligand binds the PDZ domain of the cAMP-dependent Ras GEF CNrasGEF (RAPGEF2),
  coupling Gs/cAMP to Ras activation; beta2-AR does not. PMID:12391161
• Receptor colocalizes with CNrasGEF at the plasma membrane, including in primary cortical neurons.
  PMID:12391161
• PDZ proteomic array: binds PSD-95, MAGI-2, GIPC, CAL (GOPC), SAP97 and MAGI-3; the rat V466A (paper:
  V477A, human numbering) mutation abolishes MAGI-3 binding; MAGI-3 restrains ERK1/2 activation but
  not cAMP. PMID:16316992
• MAGI-2 binding (human beta1) enhances agonist-induced internalization. PMID:11526121
• Heterodimerizes with alpha2A-AR (human). PMID:12529373
• Recycles to the plasma membrane after endocytosis. PMID:21540189

Cardiac physiology

• In mouse, cardiac inotropy and chronotropy driven by beta-agonists are mediated almost exclusively
  by beta1. PMID:10358009
• Rat atria/ventricle: noradrenaline (ICI118551 present) acts through beta1 on inotropy and I(Ca-L),
  blunted by PDE4. PMID:19133992
• Rat chromaffin cells: beta1 potentiates L-type Ca2+ current via PKA. PMID:12514203
• Rat heart rate depends on beta1 tone (atenolol bradycardia). PMID:9089896; PMID:18931026
• Cardiomyocyte hypertrophy: beta1 more effective than beta2; requires endocytosis/Src/Akt.
  PMID:18194989
• Cardiomyocyte apoptosis: beta1 (not beta2) stimulation induces apoptosis (mouse myocytes); beta1
  siRNA reduces apoptosis after MI in rat. PMID:11171998; PMID:17143192
• Greater glycogenolysis during beta1 than beta2 stimulation in perfused rat heart. PMID:17911346

Thermogenesis and metabolism

• beta1 KO mice are cold-intolerant and fail to mount diet-induced thermogenesis. PMID:22728333
• Triple beta1/2/3 knockouts are obese and cold sensitive (cannot apportion to beta1 alone).
  PMID:12387862; PMID:12161655
• Hepatocyte overexpression of beta1 or beta2 raises lipid content (rat liver aging). PMID:22457517

Nervous system

• Sleep/wake: human short-sleep ADRB1 variant; knock-in mice sleep less; ADRB1+ dorsal pons neurons
  promote wakefulness. PMID:31473062
• Memory retrieval: hippocampal beta1 required for intermediate-term contextual memory retrieval
  (mouse); BLA beta1 knockdown impairs auditory fear memory retrieval (rat). PMID:15066288; PMID:17961922
• Synaptic plasticity: beta1 agonist dobutamine rescues prefrontal LTP in malnourished rats; beta1
  paired with 5 Hz stimulation produces ERK-dependent CA1 LTP. PMID:21848869; PMID:10595521
• Presynaptic beta1 on GABAergic terminals in periaqueductal gray: beta1 antagonists increase sIPSC
  frequency. PMID:18262504
• Found in substance-P-negative large dense-core vesicles in DRG neurons. PMID:21321602

Papers with weak or indirect support for beta1

• PMID:7912752 (PVN-applied agonists and urine output): antidiuresis was mainly beta2-mediated.
  ["It was suggested that there were predominantly beta 2-adrenoceptors mediating antidiuresis in SHR."]
• PMID:11408541: zinterol (beta2) effects on I(Ca,L) were not modified by a beta1 antagonist.
• PMID:18306009: 700 microM landiolol (far above beta1 affinity) contracts trachea via Rho-kinase;
  no evidence the effect is beta1-mediated.
• PMID:21177871 (AKAP-PKA disruptor FMP-API-1): uses isoproterenol (non-selective) in rat neonatal
  cardiac myocytes and Langendorff hearts; describes the beta-AR-Gs-adenylyl cyclase-PKA cascade but
  does not discriminate beta1 from beta2. ["Stimulation of EPs with PGE1 or of β-adrenoceptors (β-AR)
  with adrenergic agonists, such as norepinephrin (NE) or isoproterenol, activates the G protein Gs,
  which in turn stimulates adenylyl cyclase (AC)."]