Question

A chemical signal can have different effects in different tissues, depending on the receptor type to which autonomic neurotransmitters and hormones bind to. For this reason, it is important to specify the signal molecule and its receptor and subtype when describing the control of a tissue. Most smooth muscle neurotransmitters and hormones bind to G-protein linked receptors. The second messenger pathways then determine the muscle response: IP3 triggers contraction and cAMP promotes relaxation.

What neurotransmitter and its GPCR triggers IP3 and contraction? Diagram/Explain the full pathway.

What neurotransmitter and its GPCR triggers cAMP and relaxation? Diagram/Explain the full pathway.

Answer 1

Acetylcholine triggers contraction of the smooth muscles when it binds to muscarinic acetylcholine receptors. This receptor is bound to the Gq class of G proteins that activate the plasma membrane bound enzyme phospholipase C-β. The activated phospholipase C cleaves phosphoinositol 4,5-bisphosphate (PIP2) to generate two secondary messengers, inositol 1,4,5-triphosphate (IP3) and Diacylglycerol (DAG). The membrane phospholipid PIP3 is a minor component of the plasma membrane, localized to the inner leaflet of the phospholipid bilayer. The secondary messenger DAG remains attached to the plasma membrane and the other secondary messenger (IP3) is released into the cytosol where it acts to signal the release of calcium ion from the endoplasmic reticulum. As a result, the the cytosolic calcium ion levels increase which increases the levels of cAMP in muscles. The pathway eventually ends up in muscle contraction.

Relaxation of smooth muscles is induced by binding of epinephrine to GPCR. Once the receptor is activated, G protein binds to it and the GDP is released from it. The place of GDP is taken up by GTP following which the receptor splits into two parts : Gα and Gβγ. Gα interacts with effector proteins leading to changes in their activity. One of the enzymes activated by Gα is adenylyl cyclase. This enzyme converts ATP into cAMP. cAMP thus produced, binds to protein kinase A (PKA) which activates phosphorylase kinase enzyme by adding phosphate groups to it. Once activated, phosphorylase kinase breaks down glycogen molecules in the muscles, thus making them relax.