Browsing Pathways

Ductal patency

The pancreas is crucial in many organisms for properly converting food into usable fuel to be used by cells. It acts as part of the digestive system for a majority of its function as it is connected to the stomach and provides digestive enzymes to the partly digested food brought in by the stomach. The pancreas also serves as an endocrine component, by creating hormones to regulate blood sugar. Insulin, a hormone created by the pancreas (beta cells), acts to lower blood sugar, which is very important as it allows cells in the body to use sugar without inducing hyperglycaemia.

G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their activity is regulated by factors that control their ability to bind to and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP). When they are bound to GTP, they are 'on', and, when they are bound to GDP, they are 'off'. G proteins belong to the larger group of enzymes called GTPases. Heterotrimeric G proteins located within the cell are activated by G protein-coupled receptors (GPCRs) that span the cell membrane. Signaling molecules bind to a domain of the GPCR located outside the cell, and an intracellular GPCR domain then in turn activates a particular G protein. Some active-state GPCRs have also been shown to be "pre-coupled" with G proteins, whereas in other cases a collision coupling mechanism is thought to occur. The G protein triggers a cascade of further signaling events that finally results in a change in cell function. G protein-coupled receptors and G proteins working together transmit signals from many hormones, neurotransmitters, and other signaling factors. G proteins regulate metabolic enzymes, ion channels, transporter proteins, and other parts of the cell machinery, controlling transcription, motility, contractility, and secretion, which in turn regulate diverse systemic functions such as embryonic development, learning and memory, and homeostasis. Receptor-activated G proteins are bound to the inner surface of the cell membrane. They consist of the Gα and the tightly associated Gβγ subunits. There are four main families of Gα subunits: Gαs (G stimulatory), Gαi (G inhibitory), Gαq/11, and Gα12/13. They behave differently in the recognition of the effector molecule, but share a similar mechanism of activation. When a ligand activates the G protein-coupled receptor, it induces a conformational change in the receptor that allows the receptor to function as a guanine nucleotide exchange factor (GEF) that exchanges GDP for GTP. The GTP (or GDP) is bound to the Gα subunit in the traditional view of heterotrimeric GPCR activation. This exchange triggers the dissociation of the Gα subunit (which is bound to GTP) from the Gβγ dimer and the receptor as a whole. Both Gα-GTP and Gβγ can then activate different signaling cascades (or second messenger pathways) and effector proteins, while the receptor is able to activate the next G protein. Gi protein alpha subunit is a family of heterotrimeric G protein alpha subunits. This family is also commonly called the Gi/o (Gi /Go ) family or Gi/o/z/t family to include closely related family members. G alpha subunits may be referred to as Gi alpha, Gαi, or Giα. Gi proteins primarily inhibit the cAMP dependent pathway by inhibiting adenylyl cyclase activity, decreasing the production of cAMP from ATP, which, in turn, results in decreased activity of cAMP-dependent protein kinase. Therefore, the ultimate effect of Gi is the inhibition of the cAMP-dependent protein kinase. The Gβγ liberated by activation of Gi and Go proteins is particularly able to activate downstream signaling to effectors such as G protein-coupled inwardly-rectifying potassium channels (GIRKs). Gi and Go proteins are substrates for pertussis toxin, produced by Bordetella pertussis, the infectious agent in whooping cough. Pertussis toxin is an ADP-ribosylase enzyme that adds an ADP-ribose moiety to a particular cysteine residue in Giα and Goα proteins, preventing their coupling to and activation by GPCRs, thus turning off Gi and Go cell signaling pathways. Activation of Gi proteins by 5-HT 1A and 1B receptors lead to the overall effect of a decrease in neuronal excitability and a potential decrease in neurotransmitter release. In Serotonin (5-HT) receptors, particularly 5-HT1 receptors, can play a role in modulating trigeminal nerve function, and their effects can vary depending on the specific receptor subtype and location within the trigeminal system. Activation of 5-HT1A receptors might lead to a decrease in the excitability of sensory neurons, potentially reducing pain perception and sensitivity to certain stimuli. 5-HT1B and 5-HT1D receptors are also found in the nervous system, including the trigeminal nerve. Activation of these receptors, typically via Gi protein signaling, can have inhibitory effects on neurotransmitter release, including the release of substances involved in pain signaling.