Second Messengers: cAMP intracellular signalling and more

[liveonearth]

--second messenger = diffusable signaling molecule produced or secreted after signal is received
--molecule activates effector proteins inside cell-->cell response to signal
--can be synthesized/released and broken down again in specific rxns
--production, storage, and destruction can be localized

SUMMARY NOTES from Anderson
--receptor-->G prot-->adenylyl cyclase-->cAMP-->protein kinase A
--nitric oxide-->guanylyl cyclase-->cGMP-->protein kinase G
--receptor-->G prot-->phospholipase C-->IP3. DAG-->protein kinase C.

TYPES
--three main types: hydrophobic, hydrophilic, and gasses
--hydrophobic: diacylglycerol, phosphatidylinositol
--hydropphilic: cAMP, cGMP, IP3, Ca2+
--gasses: nitric oxide and carbon monoxide
--cyclases = enzymes that make cyclic nucleotides
--ion channels that open
--protein kinases

HOW THEY WORK
--neurotransmitter (first messenger) binds membrane-spanning receptor protein molecule
-->receptor conformation change exposes binding site for G-protein
--G-prots are inside cell membrane, known as transducers
--when G-prot binds receptor, it can exchange a GDP (guanosine diphosphate) for a GTP (tri) molecule
--after exchange the alpha subunit of the G-protein transducer breaks free from the beta and gamma subunits
--all parts remaining membrane-bound
--alpha subunit floats around inner memb until contacts another membrane-bound protein (the primary effector)
--primary effector action-->creates a signal that can diffuse within the cell
--this signal is called the "secondary messenger"
--second messenger may activate a "secondary effector"-->changes in cell incl gene transcription

CALCIUM, PLC, IP3, DAG
--Ca2+ ions important in muscle contraction
--normally bound to intracellular components, even though a secondary messenger is a plasma membrane receptor
--Ca2+ regulates calmodulin (when bound to calmodulin is in alpha helical structure)
--enzyme phospholipase C produces diacylglycerol and inositol triphosphate
--PLC = phospholipase C, cleaves phosphatidylinositol 4,5-biphosphate (PIP2)
-->increase in inositol triphosphate (IP3) and diacylglycerol (DAG)
--IP3 binds & activates InsP3 receptor on membrane of endoplasmic/sarcoplasmic reticuli
-->opens calcium channel-->Ca2+ released into cyto/sarcoplasm-->activates another Ca2+ channel-->more Ca2+
--in smooth muscle increased Ca2+ causes contraction
--active G-protein-->opens calcium channels
--diacylglycerol-->activates protein kinase C-->assists in the activation of cAMP

cAMP SYSTEM
--glucagon===>cAMP
*--glucagon and epinephrine increase cAMP-->increase phosphorylase-->glycogenolysis
*--insulin decreases cAMP-->increased glycogen synthase and decreased phosphorylase
--receptor-->G prot-->adenylyl cyclase-->cAMP-->protein kinase A
--increase camp: beta andrenergics, H2 receptors, ACTH
--decrease camp: alpha 2 andrenergics, Muscarinic type 2 and 3 receptors (Anderson)
--neurotransmitters: Epinephrine (α2, β1, β2), Acetylcholine (M2), Dopamine (D1 D2) (Wiki)
--hormones: ACTH, ANP, CRH, CT, FSH, Glucagon, hCG, LH, MSH, PTH, TSH
--transducers: Gs (β1, β2), Gi (α2, M2)
--primary effector: Adenylyl cyclase
--secondary effector: protein kinase A

PHOSPHOINOSITOL SYSTEM
--neurotransmitters: Epinephrine (α1), Acetylcholine (M1, M3)
--hormones: AGT, GnRH, GHRH, Oxytocin, TRH
--transducer: Gp
--primary effector: phospholipase C
--secondary effectors: Ca++ release (see calcium-binding protein) and PKC (protein kinase C)

ARACHIDONIC ACID SYSTEM
--neurotransmitter: histamine
--primary effector: phospholipase A
--secondary effectors: 5-Lipoxygenase, 12-Lipoxygenase, cycloxygenase

cGMP SYSTEM
--hormones: ANP, Nitric oxide
--primary effector: guanylate cyclase
--secondary effector: protein kinase G

IP3, DAG
--alpha1, M1, M4, H1 receptors
--angiotensin receptors
--tachykinins
--endothelin

TYROSINE KINASE
--insulin
--growth factors

GENE EXPRESSION
--steroid hormones
--thyroid hormones
--retinoic acid