Autocrine system

The presence of a renal dopamine paracrine-autocrine system explains the considerable amounts of free dopamine excreted in the urine. Most derives from renal uptake and decarboxylation of circulating L-dopa and reflects the plasma levels of this amino acid and the function of the renal dopamine paracrine-autocrine system. 

Adenosine is produced by many tissues, mainly as a byproduct of ATP breakdown. It is released from neurons, glia and other cells, possibly through the operation of the membrane transport system. Its rate of production varies with the functional state of the tissue and it may play a role as an autocrine or paracrine mediator (e.g. controlling blood flow). The uptake of adenosine is blocked by dipyridamole, which has vasodilatory effects. The effects of adenosine are mediated by a group of G protein-coupled receptors (the Gi/o-coupled Ai- and A3 receptors, and the Gs-coupled A2a-/A2B receptors). Ai receptors can mediate vasoconstriction, block of cardiac atrioventricular conduction and reduction of force of contraction, bronchoconstriction, and inhibition of neurotransmitter release. A2 receptors mediate vasodilatation and are involved in the stimulation of nociceptive afferent neurons. A3 receptors mediate the release of mediators from mast cells. Methylxanthines (e.g. caffeine) function as antagonists of Ai and A2 receptors. Adenosine itself is used to terminate supraventricular tachycardia by intravenous bolus injection. 

Purines such as ATP and adenosine play a central role in the energy metabolism of all life forms. This fact probably delayed recognition of other roles for purines as autocrine and paracrine substances and neurotransmitters. Today it is recognized that purines are released from neurons and other cells and that they produce widespread effects on multiple organ systems by binding to purinergic receptors located on the cell surface. The principal ligands for... 

The factors are secreted into the extracellular milieu where they diffuse and then act in a paracrine fashion on other cells (Fig. 27-1). Indeed, there is evidence that this type of paracrine support is necessary to sustain neurons as they extend their processes over long distances in the developing nervous system [2]. An analogous process, autocrine stimulation, occurs when a cell synthesizes and secretes a growth factor to which the cell itself is responsive. In this case, the cell provides its own trophic support. 

NGF also has actions within the CNS, although it is not particularly abundant in the CNS. Its synthesis appears to be largely restricted to the hippocampus and neocortex, and even in these regions it is present at relatively low concentrations relative to the other neurotrophins. The most prominent population of NGF-responsive neurons expressing TrkA are the basal forebrain cholinergic neurons. The principal projections of these neurons are to the hippocampus and cortex, which conforms with the concept that NGF acts as a target-derived trophic factor in the CNS, just as it does in the peripheral nervous system (PNS). NGF also acts on a subpopulation of cholinergic neurons within the striatum. These interneurons express the NGF receptor, TrkA, and respond to NGF. However, they do not appear to rely entirely on NGF for their survival, and the specific actions of NGF on this neuronal population have not been clearly defined. NGF may also have autocrine actions in the CNS, as some neuronal populations have been identified that express both TrkA and NGF. 

The neurohormonal model of HF recognizes that an initiating event (e.g., acute MI) leads to decreased cardiac output but that the HF state then becomes a systemic disease whose progression is mediated largely by neurohormones and autocrine/paracrine factors. These substances include angiotensin II, norepinephrine, aldosterone, natriuretic peptides, arginine vasopressin, proinflammatory cytokines (e.g., tumor necrosis factor a, interleukin-6 and interleukin-1 ft), and endothelin-1. 

Miranda RC, Sohrabji F, Toran-Allerand CD. 1993. Neuronal colocalization of mRNAs for neurotrophins and their receptors in the developing central nervous system suggests a potential for autocrine interactions. Proc Natl Acad Sci USA 90 6439-6443. 

We currently established cultural system (amphycultural diffusion capsules) that allowed for conditions favorable for stem cell expansion in vitro. Many cell types and culture protocols and their combination with cytokines, growth factors, feeder layers can be implemented with ADC. Capsules are characterized by high perfusion rates that ensure that allow dilution of inhibitory autocrine factors and support long-term cell expansion. We have shown that ADC in vitro provides optimal cellular microenvironment that supports long term hematopoiesis (Bilko et al. 2005). 

Fig. 3.5. Endocrine, paracrine and autocrine signal transduction, a) endocrine signal transduction the hormone is formed in the specialized endocrine tissue, released into the extracellular medium and transported via the circulatory system to the target cells, b) paracrine signal transduction the hormone reaches the target cell, which is found in close juxtaposition to the hormone producing cell, via diffusion, c) autocrine signal transduction the hormone acts on the same ceU type as the one in which it is produced.

NO fulfills many criteria required to qualify as an intracellular and intercellular messenger. NO is formed with the help of specific enzyme systems activated by extracellular and intracellular signals. NO is synthesized intraceUularly and reaches its effector molecules, which may be localized in the same cell or in neighboring cells, by diffusion. Thus, it has the character of an autocrine or paracrine hormone, as well as an intracellular messenger. 

Endothelins are widely distributed in the body. ET-1 is the predominant endothelin secreted by the vascular endothelium. It is also produced by neurons and astrocytes in the central nervous system and in endometrial, renal mesangial, Sertoli, breast epithelial, and other cells. ET-2 is produced predominantly in the kidneys and intestine, whereas ET-3 is found in highest concentration in the brain but is also present in the gastrointestinal tract, lungs, and kidneys. Endothelins are present in the blood but in low concentration they apparently act locally in a paracrine or autocrine fashion rather than as circulating hormones. 

Receptor sites for angiotensin II, the main active peptide of the renin-angiotensin system, have been found in the ovaries (Lightman et al., 1989). Ovarian renin-angiotensin may also have an autocrine role in angiogenesis, steroidogenesis and oocyte maturation. Inhibin is produced by the ovarian follicle and corpus luteum (Tsonis et al.,... 

Terms in bold are defined i neuroendocrine system 882 radioimmunoassay (RIA) 884 Scatchard analysis 884 endocrine glands 886 paracrine 886 autocrine 886 insulin 887 epinephrine 888 norepinephrine 888 catecholamines 888 eicosanoid... 

---