Smooth muscle Flashcards
Where is smooth muscle found?
Vascular system
Airways
GIT
Genito-urinary tract
Which receptors and agonists mediate smooth muscle contraction?
Gq GPCRs α1-AR - Noradrenaline/A M3 - acetylcholine H1 - histamine 5HT2 - 5HT \+ prostaglandins, angiotensin, vasopressin, endothelin, substance P
How does G12/13 signalling affect smooth muscle contraction?
G12/13 -> RhoGEF -> Rho-A -> Rho K –> inhibits MLCP
Inhibits contraction
Name some muscarinic agonists that stimulate smooth muscle contraction
Pilocarpine (glaucoma)
Bethanechol (urinary retention)
What is the mechanism of smooth muscle contraction?
Free intracellular calcium increases
Calcium binds calmodulin
Calcium-calmodulin activates myosin light chain kinase which phosphorylates myosin light chain using ATP
This leads to formation of cross bridges between myosin and actin.
What causes contraction in visceral smooth muscle?
Passive stretching can trigger muscle contraction - myogenic response
Depolarisation via v-gated calcium channels
Noradrenaline, angiotensin II, endothelin, vasopressin, ergot alkaloids can bind VSM receptors and stimulate contraction
How does NA stimulate smooth muscle contraction?
Binds alpha1-adrenoceptors coupled via Gq to produce IP3 and DAG->PLC.
With cotransmitters eg ATP, neuropeptide y
What are some alpha1 antagonists?
Prazosin, indoramine
Cause vasodilation, reduce blood pressure
What is angiotensin II?
potent vasoconstrictor formed from the inactive angiotensin I by the angiotensin converting enzyme (ACE; expressed on vascular endothelial cells). Inhibited by captopril which is an anti- hypertensive drug.
Acts via ATI receptors coupled via Gq to PLC and IP3 production
What is the effect of increased cAMP in visceral smooth muscle?
relaxation
cAMP stimulates PKA, which phosphorylates and opens K-ATP channels. Hyperpolarisation closes v-gated Ca channels, decreasing MLC phosphorylation.
What is the effect of NO on muscle tone?
Increased NO activates guanylate cyclase, increasing levels of cGMP. This can activate cGMP dependent kinase, inhibit calcium entry, activate K channels and decrease IP3.
This results in relaxation / vasodilation
What are the uses of prostoglandins E2 and F2alpha in pregnancy?
These cause rhythmic contractions of the uterus. These are used in the second trimester for therapeutic abortion.
How is salbutamol used during pregnancy?
It is used to relax uterine muscle during premature labour.
How is NO synthesised?
from L-arginine via Nitric Oxide Synthase, requiring NADP
What are the three isoforms of NO?
epithelial NO - activated by Ca-CaM neuronal NO - activated by Ca-CaM - responsible for NO release from NANC neurons induced NO (induced by cytokines) - not Ca dependent
