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Pathway Description
Caffeine Vasodilation Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2022-04-08
Last Updated: 2023-10-25
Caffeine is a stimulant present in tea, coffee, cola beverages, analgesic drugs, and agents used to increase alertness. The cardiovascular effects are extensive and can help with headaches, migraines, or other types of pain in certain circumstances. Caffeine is mainly studied using coffee which has other chemicals present in it. This means that much of the research is not well understood, and there is much conflicting data on caffeine.
Regular caffeine intake can alter adenosine receptor population, especially the population of adenosine A2A receptors. It can potentially alter the potency.
Caffeine antagonizes adenosine A1 receptors in sympathetic nerves that innervate the heart muscles. Adenosine A1 receptors inhibit the release of catecholamines like norepinephrine from neurons that innervate the heart muscles. The antagonism of adenosine A1 receptors allows more norepinephrine to be released into the synapse where it causes contractions of the heart muscles through the norepinephrine subpathway. This leads to increased heartrate.
In the endothelial cells of blood vessels, caffeine, through an unknown mechanism, activates the release of calcium from the endoplasmic reticulum through the ryanodine receptor. This calcium binds to calmodulin which activates Nitric oxide synthase. This catalyzes the reaction of L-Arginine into nitric oxide. Nitric oxide then transports from the endothelial cells into the myocytes of the blood vessel located in the media. In the myocyte nitric oxide then activates Guanylate cyclase which catalyzes GTP into cGMP. cGMP activates cGMP-dependent protein kinase. Activated protein kinase has many interactions within the myocyte. Protein kinase activates potassium channels which causes potassium to leave the myocyte. This causes hyperpolarization in the cell. This prevents the voltage-gated calcium channels from opening and allowing calcium into the cell. This is also prevented by protein kinase inhibiting the voltage-gated calcium channels. This along with the activation of calcium pumps out of the cell and into the sarcoplasmic reticulum causes the cytosolic concentration of calcium to be very low. Low concentrations of calcium cannot bind to calmodulin which means calmodulin cannot activate myosin light chain kinase. With myosin light chain kinase unable to activate, myosin light chain cannot be phosphorylated which means that it is dephosphorylated by myosin light chain phosphatase. The accumulation of myosin light chain causes myosin to unbind from actin and the muscle to relax. The relaxation of smooth muscles around blood vessels causes vasodilation. This effect is observed in the majority of the body except the head and neck.
The opposite effects of caffeine is called the coffee-effect and based on the population of receptors in that area of the body, as well as their affinity for caffeine. This causes vasodilation in the majority of the human body, but vasoconstriction in the head and neck.
References
Caffeine Vasodilation Pathway References
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