AID and RPA: PKA makes the connection local

Local anesthetics (LAs) block sensory and motor impulses by inhibiting the sodium channels on the nerve cell membranes. This induces temporary loss of sensation, relieving pain in a specific body area.
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...

The potency and duration of action of local anesthetics (LAs) are determined by their pharmacokinetics. Pharmacokinetics describes how LAs are absorbed, distributed, metabolized, and eliminated from the body. When administered to the vascular tissues, LAs are quickly absorbed and enter the systemic circulation, reducing their localized effects. Adding vasoconstrictors such as epinephrine to LAs reduces their absorption into the systemic circulation, making them clinically effective. The...

Intravenous regional anesthesia or the Bier block technique is used to anesthetize a specific limb or extremity. It uses exsanguinated or blood-drained vessels to transport local anesthetics or LAs to the peripheral nerve trunks. Lidocaine without vasoconstrictors like epinephrine is most commonly used for this technique. Other drugs used are prilocaine, ropivacaine, and chloroprocaine. Bupivacaine is not recommended for this technique due to its high cardiac toxicity.
One of the advantages of...

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...

ATP-driven pumps, also known as transport ATPases, are integral membrane proteins. They have binding sites for ATP located on the membrane's cytosolic side and the ion-conducting domain in the transmembrane region. These pumps use the free energy released from ATP hydrolysis to move the solutes across cell membranes against an electrochemical gradient.
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and are...

The P-type pumps are a large family of integral membrane transporter ATPases. They are divided into five major types based on substrate specificity, from I to V.
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...