Adrenergic receptors (ARs) are expressed in almost all organs and tissues and
regulate a large number of diverse physiological processes upon activation by
epinephrine and norepinephrine. There are three families of ARs, a1, a2, and
b-ARs, with distinct pharmacological properties and functions. Since the first
identification of bARs more than three decades ago, research on ARs has led to
the establishment of many fundamental concepts in G protein-coupled receptor
During the past two decades, reductionist biological science has generated new
empirical data on the molecular foundations of biological structure and function
at an accelerating rate. The list of organisms whose complete genomes have been
sequenced is growing by the week. Annotations of these sequences are becoming
more comprehensive, and databases of protein structure are growing at impressive,
indeed formerly unimaginable rates.
VEGF and its receptors are required for vasculogenesis (the de novo formation of blood vessels from differentiating endothelial cells, as occurs during embryonic development) and angiogenesis under normal (wound healing, corpus luteum formation) and pathologic processes (tumor angiogenesis, inflammatory conditions such as rheumatoid arthritis).
It has been nearly 20 years since the last Humana Press book devoted to
serotonin (5-hydroxytryptamine; 5-HT) receptors has appeared. Since then, the
field of 5-HT receptors has undergone a revolution due to the discovery of many
additional 5-HT receptors. Although 5-HT was chemically elucidated in 1948 by
Page and colleagues (Rapport et al.
The Adipocyte and Adipose Tissue Adipose tissue is composed of the lipid-storing adipose cell and a stromal/vascular compartment in which cells including preadipocytes and macrophages reside. Adipose mass increases by enlargement of adipose cells through lipid deposition, as well as by an increase in the number of adipocytes. Obese adipose tissue is also characterized by increased numbers of infiltrating macrophages.
Imatinib has also demonstrated targeted activity in other diseases, including gastrointestinal stromal tumors (GIST), rare mesenchymal tumors of the GI tract (stomach and small intestine). The pathogenic molecular event for most patients with this disease is mutation of the proto-oncogene c-Kit, leading to the constitutive activation of this receptor tyrosine kinase without the binding of its physiologic ligand, stem cell factor. About 10% of GISTs encode activating mutations of the PDGFRα instead of c-Kit.
Estrogen receptors (ERs) and androgen receptors, members of the steroid hormone family of nuclear receptors, are targets of inhibition by drugs used to treat breast and prostate cancers, respectively. Tamoxifen, a partial agonist and antagonist of ER function, can mediate tumor regression in metastatic breast cancer and can prevent disease recurrence in the adjuvant setting, saving thousands of lives each year. Tamoxifen binds to the ER and modulates its transcriptional activity, inhibiting activity in the breast but promoting activity in bone and uterine epithelium.
The bevacizumab experience suggests that inhibition of the VEGF pathway will be most efficacious when combined with agents that directly target tumor cells. This also appears to be the case in the development of small-molecule inhibitors (SMI) that target VEGF receptor tyrosine kinase activity but are also inhibitory to other kinases that are expressed by tumor cells and important for their proliferation and survival.
Dopamine D4receptors (D4Rs) are G protein-coupled receptors that play a
role in attention and cognition. In the present study, we investigated the
dimerization properties of this receptor. Western blot analysis of the
human D4.2R, D4.4R and D4.7R revealed the presence of higher molecular
weight immunoreactive bands, which might indicate the formation of
receptor dimers and multimers.
Atrial natriuretic peptide (ANP), via its guanylyl cyclase A (GC-A) recep-tor and intracellular guanosine 3¢,5¢-cyclic monophosphate production, is
critically involved in the regulation of blood pressure. In patients with
chronic heart failure, the plasma levels of ANP are increased, but the car-diovascular actions are severely blunted, indicating a receptor or postrecep-tor defect.
Unusually among ATP-binding cassette proteins, the sulfonylurea receptor
(SUR) acts as a channel regulator. ATP-sensitive potassium channels are
octameric complexes composed of four pore-forming Kir6.2 subunits and
four regulatory SUR subunits. Two different genes encode SUR1 (ABCC8)
and SUR2 (ABCC9), with the latter being differentially spliced to give
SUR2A and SUR2B, which differ only in their C-terminal 42 amino acids.
arco(endo)plasmic reticulum calcium ATPase (SERCA)2b maintains the
homeostasis by transferring Ca
from the cytosol to the
lumen of the endoplasmic reticulum (ER). Recently, SERCA2b has also
been shown to be involved in the biosynthesis of secreted and membrane
proteins via direct protein–protein interactions, involving components of
the ER folding and quality-control machinery, as well as newly synthesized
G protein-coupled receptors.
This book, with its 16 chapters, documents the present state of knowledge of the
adenosine A3 receptor. It covers a wide range of information, including data from
studies of theoretical, molecular and cellular pharmacology, signal transduction,
integrative physiology, new drug discoveries and clinical applications. It fills an
important gap in the literature since no alternative source of such information is
TheTorpedonicotinic acetylcholine receptor is a heteropentamer (a2bcd)in
which structurally homologous subunits assemble to form a central ion
pore. Viewed from the synaptic cleft, the likely arrangement of these sub-units isa–c–a–d–blying in an anticlockwise orientation.
Palmitoylcarnitine, known to promote differentiation of neuroblastoma
NB-2a cells as well as to inhibit protein kinase C (PKC) activity and to
decrease phorbol ester binding, was shown previously to diminish the
amount of complex formed between PKCdand its substrate GAP-43. In
the present work we studied the effect of palmitoylcarnitine on the inter-action between PKCbII and its receptor RACK1.
a-Conotoxins are small peptides from cone snail venoms that function as
nicotinic acetylcholine receptor (nAChR)-competitive antagonists differenti-ating between nAChR subtypes. Current understanding about the mechan-ism of these selective interactions is based largely on mutational analyses,
which identify amino acids in the toxin and nAChR that determine the
energetics of ligand binding.
Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-1
(SHP-1) is a critical inhibitory regulator in T cell-receptor (TCR) signaling.
However, the exact molecular mechanism underlying this is poorly defined,
largely because the physiological substrates for SHP-1 in T cells remain
A central pathway through which leptin acts to regulate appetite and body weight. Leptin signals through proopiomelanocortin (POMC) neurons in the hypothalamus to induce increased production of α-melanocyte-stimulating hormone (α-MSH), requiring the processing enzyme PC-1 (proenzyme convertase 1). α-MSH acts as an agonist on melanocortin-4 receptors to inhibit appetite, and
the neuropeptide AgRp (Agouti-related peptide) acts as an antagonist of this receptor. Mutations that cause obesity in humans are indicated by the solid green arrows.
Prostaglandin (PG) F2asuppresses adipocyte differentiation by inhibiting the
function of peroxisome proliferator-activated receptor c. In this study, we
identified a novel suppression mechanism, operating in the early phase of
adipogenesis, that increased the production of anti-adipogenic PGF2a and
PGE2by enhancing cyclooxygenase (COX) 2