User:M.margaret.m/sandbox

Affective sensation is a sensation accompanied with a strong compulsion to act on it. Most often in neuroscience, it refers to the emotional sensibility in response to affective stimuli of a particular valence. It is transmitted via the spinothalamic tract through the spinal cord, and can be associated with reflex actions such as the scratch reflex, gag reflex or the withdrawal reflex. Sensory processing of the brain interacts with behavioral choices such as decisions to eat or stop eating in healthy individuals and in people with eating disorders.[1 ]

Background and Mechanism
Affective sensory information is transmitted via the spinothalamic tract. The sensation information is then accompanied by a compulsion to act. For instance, the bottom-up approach would have an itch accompanied by the need to scratch, and a painful stimulus inducing the desire to withdraw from the pain.

The location of the spinothalamic tract is important clinically due of the characteristic sensory deficits that follow certain spinal cord injuries. For instance, a unilateral spinal lesion will produce sensory loss of touch, pressure, vibration, and proprioception below the lesion on the same side. The pathways for pain and temperature, however, cross the spinal cord midline to ascend on the opposite side of the cord. Therefore, diminished sensation of pain below the lesion will be observed on the side opposite the mechanosensory loss and the lesion.

Affect
Affective sensation deals with response-emotionality and is distinct from presentative, or neutral, sensation. This is due to affective stimuli which can have positive, negative, or neutral valence. These stimuli can be sensed individually as well as in an integrated manner such that positive and negative affective stimuli can be combined to influence experiential affective sensation and response. In the case of combination, recency and contrast effect s on overall affect are influential such that, for example, a negative stimuli followed by a positive stimuli yields an overall positive affect.

Emotional Sensing
Subjective well-being draws from both cognitive and affective components, combining general evaluations of ones' life with overall affective sensative-impressions. Neural measures of affective quality of life have been positively correlated with greater left alpha activity in the superior PFC, gray matter volume in multiple prefrontal cortices, spontaneous activity in the right amygdala, and even emotional intelligence. Those with affective disorders may also demonstrate differences in affective sensation as a result of mood-dependent alterations in brain arousal regulation, especially seen between those with mania, depression, and those without the disorder. Negative affectivity tends to be related to greater levels of social anxiety, anxious arousal, and anxiety sensitivity.

Physical and Mental Modulation
Physical pathological sensation, as occurs in IBS, COPD, and other illnesses, is also influential in affective sensation and response. The emotional response to especially a chronic illness can be correlated with its severity. This has been shown in COPD, where emotionally-driven descriptions of sensation due to breathing impairments may reflect the severity of the illness and probability of long-term, responsal behavior changes. Additionally, in IBS patients, affective sensation and its correlative brain areas including the ACC, insula, and VMPFC demonstrated heightened fMRI activity in response to painful visceral stimuli, and an inability to down-regulate their activation and modulate the emotional response to pain. This link between perceptual intensity and affective sensation persists in the case of chili pepper consumption. Those individuals who eat chili peppers more often, and presumably enjoy them, also report less burning sensation in response to eating chilis. While this could be due to either individual taste-perception differences or intensity judgement differences, it is more likely due to the latter because previous spicy food-consumption experiences do not correlate with the differences in affective sensation responses.

Taste Sensation
Affective sensation can also be modulated using the top-down approach with cognitive factors influencing hedonic experience, such as with soup labeled "rich and delicious" inducing greater positive affect than when labeled "boiled vegetable water." This modulation can be seen in the orbitofrontal cortex and pregenual cingulate cortex. Taste serves to identify potential nutrients and toxins. For example, when one tastes a potentially nutritious stimulus, the connectivity between the insula and a feeding network including the hypothalamus, ventral pallidum, and striatum is greater than when tasting a potentially harmful stimulus. These results support the existence of an integrated supramodal flavor system in the anterior ventral insula that preferentially communicates with the circuits guiding feeding when the flavor is potentially nutritive.

ACTH receptor... publish wiki in bold, my changes in italics

The adrenocorticotropic hormone receptor or ACTH receptor also known as the melanocortin receptor 2 or MC2 receptor is a type of melanocortin receptor (MCR) (type 2) which is specific for ACTH.[3]

It is a G-coupled receptor located on the external cell plasma membrane, and plays a role in immune function and glucose metabolism.

Structure: ACTH receptors are the shortest of the melanocortin receptor family and are the smallest known G-coupled receptors. '''Both human and bovine ACTH receptors are synthesized as 297 residue long proteins. There is 81% homology between human and bovine sequences.[4] The full length sequence includes seven hydrophobic domains that are predicted as transmembrane segments.[4] In the third intracellular loop of the receptor a protein kinase A and protein kinase c phosphorylation motifs have been detected.[4]''' ACTH receptors also require the binding of melanocortin-2 receptor accessory protein-1 (MRAP1) without which ACTH receptors cannot bind ACTH. Without MRAP, the receptor is degraded in the endoplasmic reticulum, but with MRAP, the receptor is glycosylated and expressed on the cell plasma membrane.

Ligands: MCR's have both endogenous agonists and antagonists.

Agonists: ''α-MSH and ACTH are both peptides derived from processed POMC, and both activate the other MCR's, but ACTH is the only agonist ligand for MC2R. This suggests that there is more protein-related specificity for binding MC2R.''

Antagonists: Agouti-related protein and Agouti-signaling protein are antagonist peptides to MC2R.

Tissue and subcellular localization: 'ACTH receptor is primarily'' found in the zona fasciculata of the human adrenal cortex. Binding of the receptor by ACTH stimulates the production of gluccocorticoids  cortisol. (By contrast, aldosterone production from the zona glomerulosa is stimulated primarily by angiotensin II.)' ACTH receptors are also expressed in the skin, and in both white and brown adipoctyes, and is expressed in greater concentrations when adipose cells differentiate.''

'''Protein recognition at the receptor uses energy obtained from the dephosphorylation of ATP to cAMP by adenylate cyclase. ACTH receptors are located on the plasma membrane, and are G protein-coupled rece ptors.'''

The ACTH receptor uses cAMP as a secondary messenger.[5][6] When bound, the receptor couples to G-protein alpha subunit, activates adenylyl cyclase, and increases cAMP production.

''It is well known that levels of corticosterone (CORT) secretion demonstrate a circadian rhythm, highly regulated by effects of the suprachiasmatic nucleus, with higher levels in the early evening and lower levels in the morning. ACTH levels, ACTH receptor expression, and MRAP1 expression also demonstrate circadian rhythm, with ACTH secretion and MRAP expression highest in the evening, suggesting that MRAP expression is responsible for CORT secretory regulation. However, with exposure to constant light, the rhythmic expression of the ACTH receptor and MRAP genes reversed, suggesting ACTH-independent signalling pathways for MRAP and ACTH receptor transcription and expression.''

Clinical Significance Pathology:

''The ACTH receptor plays a role in glucose metabolism when expressed in white adipose cells. When bound to ACTH, a short-term insulin-resistance occurs, and it stimulates lipolysis via hormone sensitive lipase. Demonstrated in mice, ACTH promotes lipolysis in response to increased energy demand, notably in times of stress. Lipolytic activity due to melanocortin receptors has been demonstrated in several types of test animals: rats and hamsters primarily respond to ACTH, rabbits respond to alpha and beta MSH's (therefore not using the ACTH receptor), and guinea pigs responding to both ACTH and other MSH's. In humans, ACTH has little lipolytic effect on adipose tissue.''

ACTH receptor activation also influences immune function. ''Melanocortins, including ACTH, have anti-inflammatory effects which can be exerted via glucocorticoid(GC)-dependent and -independent pathways. The GC-dependent pathway activates ACTH receptors to increase levels of cortisol which bind GC receptors. Via genomic and faster non-genomic pathways, this causes, among other immune responses, a reduction in leukocyte and neutrophil infiltration, cytokine production, especially of cytokine CXCL-1, and increase phagocytosis of apoptotic neutrophils. These profound anti-inflammatory effects and the ability to increase GC's are why ACTH therapy is still used today. It is often used as treatment for infantile spasms, multiple sclerosis, nephrotic syndrome, gout, ulcerative colitis, Crohn's disease, rheumatoid arthritis, and systemic lupus erythematosus. This is problematic long-term and can lead to ACTH-receptor pathway-related side effects including: Cushing's syndrome, fluid retention, glaucoma, and cardiovascular disorders. ''

Mutations in this receptor cause familial glucocorticoid deficiency (FGD) type 1, in which patients have high levels of serum ACTH and low levels of cortisol.[7][8] ''Mutation of the receptor gene causes 25% of FGD, and mutation on the MRAP gene causes 20% of FGD. Mutations of ACTH can also contribute to this pathology: mutation of the "message sequence" inhibits cAMP production when bound to the ACTH receptor, and mutation of the "address sequence" inhibits binding to the receptor altogether.''

Later: