Cavk Synthesis

Contractility of ASM requires an increased levels of intracellular Ca2+. When surface receptors are not activated, Ca2+ levels are low. Upon activation of these cell surface receptors by contractile agonists e.g. acetylcholine, serotonin and histamine, intracellular Ca2+ increases causing a contraction (9). Smooth muscle cell contraction is controlled by both receptor and mechanical activation of proteins actin and myosin and also changes to membrane potential.

From molecular perspective, hyperforin has multidirectional mechanisms of action. It acts on ligand-gated (GABA, NMDA and AMPA receptors) (29, 30) and voltage-gated channels (Ca2+, K+, and Na+) (29, 31). In contrast to blockade of ion transport through the plasma membrane, hyperforin can increased an inward Ca2+ current. These processes are dose dependent and probably involved a few different cellular events. In the details, hyperforin in in vitro studies increased the Ca2+ intracellular level by activation of the non-selective canonical transient receptor potential 6 channels (TRPC6) or by the releasing Ca2+ from mitochondria (32–34). As has been previously shown hyperforin activates intracellular

​Cystic fibrosis is an inherited, chronic disease of the secretory glands which directly affects the lungs and digestive system (NLM, 2015). To look more closely at a cellular level, there is a defective gene in which their protein product that regulates movement of sodium

The CF gene is found in Chromosome 7. Mutations in the CFTR gene cause cystic fibrosis. This protein functions as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes The CFTR gene provides instructions for making a channel that transports negatively charged particles called chloride ions into and out of cells. Chloride is a component of sodium chloride, a common salt found in sweat. The official name of this gene is “cystic fibrosis transmembrane conductance regulator “or

Voltage gated channels are necessary components of life processes, in many organisms. One in particular, is the calcium voltage gated ion channel. Often lodged within the phospholipid bilayer, the imbalance of the calcium, or, the inside vs outside concentration, creates a gradient. The channel proteins often undergo conformations, states that which allow or block calcium ions from passing through. As ions move inside the cell, this creates a depolarization, or surge in the voltage. Clinically, this is associated with the heart and how it allows the heart to contract, which can be read in the

Cystic fibrosis is caused by defects in the cystic fibrosis transmembrane conductor regulator (CFTR) gene, which codes for the CFTR protein (Sartin, 2013). The CFTR protein is a chloride channel present in secretory glands and the epithelial cells of numerous organs. Due to the high affinity of chloride, sodium and water, CFTR protein plays a vital role in the homeostatic

The discovery of therapeutic molecules that target the underlying cause of Cystic Fibrosis, rather than the symptoms, has transformed the approach of cystic fibrosis treatments. Two such sets of drugs are classed as correctors and potentiators. The latter set aim to target and augment the function of the mutated CFTR channel that is present on the membrane. Class III and IV CFTR mutations benefit from this approach as they are defined as mutated CFTR channels that, although present on the apical membrane, exhibit decreased, or no functional activity compared to functional CFTR channels. Class III mutations are missense mutations that result in a reduce open time of the CFTR channels. This severe class of mutations include G551D and S549R

Mutation of the Cystic Fibrosis gene affects the protein responsible for movement of chloride ions through the cell membranes (3). This protein is called CFTR, cystic fibrosis transmembrane regulator (3). CFTR is located on chromosome 7 and is 250 kilobases long. CFTR has about 1900 mutations that are split up into six classes (6). Common classes are class I that are stop mutations and class II (6). Class II are mutated CFTR that are recognized as abnormal by the cell’s “control system”; the most common mutation for Cystic Fibrosis belongs to this class (6). CFTR is present in cells at the passageways of lungs, pancreas, colon and genitourinary tract (3). More specifically, the mutation that causes Cystic Fibrosis has a deletion of three base pairs in the gene (3). There are 400 plus mutations responsible for causing Cystic Fibrosis as of 1995 (3).

Cystic fibrosis (CF) is a progressive condition in which epithelial exocrine glands are obstructed (Howe, 2001). Whilst many organs and bodily systems are disrupted by CF, the lungs and gastrointestinal organs are predominantly affected; it is also most common amongst the Caucasian population due to the autosomal recessive gene (Quitter et al., 2003 cited in Wolfe & Mash, 2006, pg 514). The faulty gene effects the production of cystic fibrosis transmembrane conductance regulator protein, which is responsible for the formation of molecular tunnels which monitor the movement of salts and water from the cells (Hopkin, 2010 pg 4).

The Cystic Fibrosis Gene codes for a protein called cystic fibrosis transmembrane conductance regulator produced in the epheilial cells. The CFTR protein acts as channel in the membrane of cells that produce mucus, sweat, saliva, tears, and digestive system. This channels transport chloride ions in and out of the cell, because the chloride ions help control the movement of water in the tissue of the human body, in a process called diffusion. This process necessary to the production of mucus, mucus is a slippery substance that lubricates and protects the lining of the lung airways, digestive systems, reproductive systems, and organs and tissues. However, when a person inherits mutated CFTR gene,

When both NA and Praz act on GPCR in VSM membrane, NA induces production of IP3 and Praz does not. Therefore, to produce same level of contraction from NA only by using NA with Praz, higher concentration of NA is necessary to occupy more receptor. Theoretically, the maximum (100%) concentration should be achieved with high concentration of agonist with antagonist (1 p10). 82.61% of contraction was observed in this experiment. it could be due to tissue damage from experimental process or could be influenced by more than five days storage of prepared tissue (3). 5HT2 receptor is located in the CNS and also located in the periphery (1 p196). The subtypes of 5HT2 are linked to colonic motility (5-HT2A), heart (5-HT2B), and central nervous system (5-HT2c) (1 p196). Meth act as antagonist to 5-HT2A, partial agonist to 5-HT2B, and antagonist to 5-HT2C (1 p199, 4). Both 5HT, and Meth works as agonist, but binding of 5HT to receptor give full response (full agonist), and Meth give less than full response (partial agonist). Meth act as agonist in presence of low concentration of 5HT with Meth. Meth act as antagonist in presence of high concentration of 5HT with Meth. Meth disturbs 5HT binding to receptor to give full response. Therefore, crossover of 5HT only trend line and 5HT with Meth should be observed. Absence of crossover might be due to different efficacies, as Meth is known

The cause of Cystic Fibrosis is mutations in a single gene on chromosome 7 that encodes for the cystic fibrosis transmembrane regulator , CFTR. The mutated CFTR gene in Cystic Fibrosis patients causes a defective chloride ion pathway. Typically, a functioning chloride transport allows chloride, which produces mucus, to exit the cells. Also, a chloride transport helps

Cystic Fibrosis (CF) is an autosomal recessive gene that causes a wide range of symptoms because there are over 1,000 changes or mutations that can occur within the cystic fibrosis transmembrane receptor (CFTR) protein. The CFTR protein is generally a chloride ion chain “regulated by cyclic adenosine monophosphate and therefore can act as a regulator of other electrolyte channels”(Grossman, S., & Grossman, L. 2005, p. 46). Typically this protein allows chloride ions to exit mucus-producing cells allowing water to flow in and thin the mucus. However, if the CFTR protein has been mutated, such as in cystic fibrosis, chloride ions cannot exit. This causes the mucus to thicken, become sticky, and obstruct the various channels it passes through. This build up of mucus also prevents bacteria from being cleaned from cells thoroughly increasing the patients risk for infections (Grossman, S., & Grossman, L. 2005). However, the severity of CF depends on whether the patients have complete or partial loss of the CFTR gene. If the person has the classic form of CF abnormalities of CFTR will commonly affect “…the respiratory, gastrointestinal, endocrine and metabolic, and genitourinary systems”(Schram, C. 2012). However, if people have atypical forms of CF their genetic disorder may only affect one of the organ systems and may not be found until the patient develops symptoms in their late childhood, early adolescence, or adulthood

Cystic fibrosis (CF) is a disease of exocrine gland function that involves multiple organ systems but chiefly results in chronic respiratory infections, pancreatic enzyme insufficiency, and associated complications in untreated patients. CF is the major cause of severe chronic respiratory disease in children, and it is an autosomal recessive disorder involving the exocrine glands. According to Bye (2016), this disorder is caused by mutations in the CF transmembrane conductance regulator protein, which normally functions to regulate the transepithelial ion flow critical to maintaining the proper ionic composition and volume of airway surface fluid.

According to Riordan et al. (1989), the gene responsible for CF was discovered by Collins, Tsui and colleagues in 1989. During the night after Tsui and Collins attended a gene-mapping workshop, they are hunting for the cause of CF. They found out that there is a gene that might have a role in transporting ions through cell membranes by looking from its sequence. Then they received a fax which mentioned that most of affected people is lacking three base pairs from both copies of this gene whereas those unaffected person