Hormone receptor sites

Inositol triphosphate (IP3)-gated channels are also associated with membrane-bound receptors for hormones and neurotransmitters. In this case, binding of a given substance to its receptor causes activation of another membrane-bound protein, phospholipase C. This enzyme promotes hydrolysis of phosphatidylinositol 4,5-diphosphate (PIP2) to IP3. The IP3 then diffuses to the sarcoplasmic reticulum and opens its calcium channels to release Ca++ ions from this intracellular storage site. 

The acute CNS effects of MDMA administration are mediated by the release of monoamine transmitters, with the subsequent activation of presynaptic and postsynaptic receptor sites.40 As specific examples in rats, MDMA suppresses 5-HT cell firing, evokes neuroendocrine secretion, and stimulates locomotor activity. MDMA-induced suppression of 5-HT cell firing in the dorsal and median raphe involves activation of presynaptic 5-HT1A autoreceptors by endogenous 5-HT.4142 Neuroendocrine effects of MDMA include secretion of prolactin from the anterior pituitary and corticosterone from the adrenal glands 43 Evidence supports the notion that these MDMA-induced hormonal effects are mediated via postsynaptic 5-HT2 receptors in the hypothalamus, which are activated by released 5-HT. MDMA elicits a unique profile of locomotor effects characterized by forward locomotion and elements of the 5-HT behavioral syndrome such as flattened body posture, Straub tail, and forepaw treading.44 6 The complex motor effects of MDMA are dependent on monoamine release followed by activation of multiple postsynaptic 5-HT and DA receptor subtypes in the brain,47 but the precise role of specific receptor subtypes is still under investigation. 

In a very broad overview of the structural categories one can state several statistical correlations with type of function. Hemes are almost always bound by helices, but never in parallel a//3 structures. Relatively complex enzymatic functions, especially those involving allosteric control, are occasionally antiparallel /3 but most often parallel a//3. Binding and receptor proteins are most often antiparallel /3, while the proteins that bind in those receptor sites (i.e., hormones, toxins, and enzyme inhibitors) are most apt to be small disulfide-rich structures. However, there are exceptions to all of the above generalizations (such as cytochrome cs as a nonhelical heme protein or citrate synthase as a helical enzyme), and when one focuses on the really significant level of detail within the active site then the correlation with overall tertiary structure disappears altogether. For almost all of the dozen identifiable groups of functionally similar proteins that are represented by at least two known protein structures, there are at least... 

The relationship between the structure of a series of peptides derived from the adrenocorticotropic hormone ACTH, and the behavioural activity in an active avoidance behaviour test, has been studied over the past 10-20 years. The results obtained were quite different from those in which endocrine activity relationships were studied. From the outcome of a quantitative study on the structure--behavioural activity of the ACTH-related peptides, suggestions about the spatial interactions at the receptor site were made. This receptor-bound conformation differed from those suggested by solution experiments or found in crystal structures. 

Mechanism of Action An antipsychotic that blocks postsynaptic dopamine receptor sites in brain. Has alpha-adrenergic blocking effects, and depresses the release of hypothalamic and hypophyseal hormones. Therapeutic Effect Suppresses psychotic behavior. 

The AChR is one of the best characterized of all cell-surface receptors for hormones or neurotransmitters (Figure 2-9). One form of this receptor is a pentamer made up of four different polypeptide subunits (eg, two chains plus one B, one 7, and one 5 chain, all with molecular weights ranging from 43,000 to 50,000). These polypeptides, each of which crosses the lipid bilayer four times, form a cylindrical structure that is 8 nm in diameter. When acetylcholine binds to sites on the subunits, a conformational change occurs that results in the transient opening of a central aqueous channel through which sodium ions penetrate from the extracellular fluid into the cell. 

Experimental studies have documented changes in drug response caused by increases or decreases in the number of receptor sites or by alterations in the efficiency of coupling of receptors to distal effector mechanisms. In some cases, the change in receptor number is caused by other hormones for example, thyroid hormones increase both the number of 3 receptors in rat heart muscle and cardiac sensitivity to catecholamines. Similar changes probably contribute to the tachycardia of thyrotoxicosis in patients and may account for the usefulness of propranolol, a 3-adrenoceptor antagonist, in ameliorating symptoms of this disease. 

Large numbers of thyroid hormone receptors are found in the most hormone-responsive tissues (pituitary, liver, kidney, heart, skeletal muscle, lung, and intestine), while few receptor sites occur in hormone-unresponsive tissues (spleen, testes). The brain, which lacks an anabolic response to T3, contains an intermediate number of receptors. In congruence with their biologic potencies, the affinity of the receptor site forT4 is about ten times lower than that forT3. Under some conditions,... 

A variety of signals can be transmitted across membranes without the actual flow of a substance from one side of the membrane to the other. We saw in chapter 12 that some hormones bind to specific receptor sites on the outer surface of the plasma membrane, thereby triggering metabolic changes on the cytosolic side of the membrane. Hormonal systems that function in this way are discussed in greater detail in chapter 24. Other membrane proteins mediate specific cell-cell interactions. Sometimes these interactions merely stimulate particular types of cells to bind to one another, but often they also trigger reactions that result in proliferation or differentiation of the interacting cells. We discuss signals of this type when we consider the interaction between the B and T cells of the immune system (see Supplement 3). 

The mechanisms of weight gain are not known. Olanzapine, for example, affects at least 19 different receptor sites, may have reuptake inhibition properties, and may affect hormones such as prolactin. Animal... 

When TSH contacts its receptor-sites located throughout the thyroid gland a series of enzymic reactions occur using tyrosine and iodine as substrates or raw materials to produce and/or release L-Thyroxine (T-4). This is then released into the vascular system so it can circulate. It should be noted that T-4 is an active form of thyroid hormone. 

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