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 called ...

-related

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

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 and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

and gastrointestinal tract.

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).

Function

Neuromedin regulates the following functions: *

exocrine Exocrine glands are glands that secrete substances on to 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 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 (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 p ...

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 heterotrimeric complex. The biggest non-structu ...

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 market value of all the final goods and services produced and sold (not resold) in a specific time period by countries. Due to its complex and subjective nature this measure is ofte ...

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. cAMP activates of the enzyme

Protein Kinase A In cell biology, protein kinase A (PKA) is a family of enzymes 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, including regulatio ...

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

CREB binding protein Cyclic adenosine monophosphate Response Element Binding protein Binding Protein (CREB-binding protein), also known as CREBBP or CBP or KAT3A, is a coactivator encoded by the ''CREBBP'' gene in humans, located on chromosome 16p13.3. CBP has intrin ...

, 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