Neuromedin B (NMB) is a

bombesin Bombesin is a 14-amino acid peptide originally isolated from the skin of the European fire-bellied toad (''Bombina bombina'') by Vittorio Erspamer ''et al.'' and named after its source. NIHMSID 45053. It has two known homologs in mammals call ...

-related

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

in mammals. It was originally purified from pig spinal cord, and later shown to be present in human

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

and

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

Sequence

The sequence of the C-terminal decapeptide is highly conserved across mammalian species: GNLWATGHFM-(NH2); this decapeptide is sometimes noted as neuromedin B, but it is more accurately described as neuromedin B 23-32. The sequence of neuromedin B (in rat) is: TPFSWDLPEPRSRASKIRVHPRGNLWATGHFM-(NH2). The (NH2) here indicates a post-translational modification -- alpha amidation of the carboxy terminus.

Function

Neuromedin regulates the following functions: *

exocrine Exocrine glands are glands that secrete substances onto an epithelial surface by way of a duct. Examples of exocrine glands include sweat, salivary, mammary, ceruminous, lacrimal, sebaceous, prostate and mucous. Exocrine glands are one of t ...

and

endocrine The endocrine system is a messenger system in an organism comprising feedback loops of hormones that are released by internal glands directly into the circulatory system and that target and regulate distant organs. In vertebrates, the hypotha ...

secretions * cell growth * body temperature * blood pressure and glucose level * sneezing

Neuromedin signaling pathway

NMB acts by binding to its high affinity cell surface receptor,

neuromedin B receptor The neuromedin B receptor (NMBR), now known as BB1 is a G protein-coupled receptor whose endogenous ligand is neuromedin B. In humans, this protein is encoded by the ''NMBR'' gene. Neuromedin B receptor binds neuromedin B, a potent mitogen an ...

(NMBR). This receptor is a

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...

with seven transmembrane spanning regions, hence the receptor is also denoted as a 7-transmembrane receptor (7-TMR). Upon binding several intracellular signaling pathways are triggered (see Figure 2). When NMB binds to its 7-TMR, the

heterotrimeric G protein Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a Heteromer, heterotrimeric complex. The biggest no ...

that is attached to the receptor is activated. The G-protein is called heterotrimeric because it consists of 3 polypeptides: α subunit, β subunit, and γ subunit. In the activated NMBR/G-protein complex, there occurs an exchange of GTP for

GDP Gross domestic product (GDP) is a monetary measure of the total market value of all the final goods and services produced and rendered in a specific time period by a country or countries. GDP is often used to measure the economic performance o ...

bound to G-α subunit. The G-α subunit, in turn, dissociated form the G-βγ subunits. The free G-α inactivates

adenylate cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...

(AC), which, in turn, catalyzes the conversion of ATP to cAMP, the latter of which functioning as a

second messenger Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form of cell signaling, encompassing both first m ...

. cAMP activates of the enzyme

Protein Kinase A In cell biology, protein kinase A (PKA) is a family of serine-threonine kinases whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, in ...

(PKA). PKA enters the nucleus and activates the cAMP response element-binding protein. The activated CREB binds along with

CREB binding protein CREB-binding protein, also known as CREBBP or CBP or KAT3A, (where CREB is cAMP response element-binding protein) is a coactivator encoded by the ''CREBBP'' gene in humans, located on chromosome 16p13.3. CBP has intrinsic acetyltransferase funct ...

, co-activator to the CRE region of the DNA in the nucleus. CREB and CBP are held together by

leucine zipper A leucine zipper (or leucine scissors) is a common three-dimensional structural motif in proteins. They were first described by Landschulz and collaborators in 1988 when they found that an enhancer binding protein had a very characteristic 30-amin ...

s. CRE is the control that activates number of growth factors, and thus cell proliferation and some anti-apoptotic genes. In the brain, CREB plays a role in long-term memory and learning.

References

External links

* {{Neuropeptides Neuropeptides