Paracrine system

Fig. 5. Schematic representation of a possible vitamin D paracrine system in cells from hematopoietic lineage.

Some of the receptors defined on the gastric endocrine/paracrine system. The ECL and G cells upregulate acid secretion, and the D cell inhibits acid secretion. The ECL cell expresses the CCKj or gastrin receptor and the somatostatin type 2 receptor and PAC1, the PACAP receptor. The G cells express a stimulatory muscarinic receptor subtype not known and a stimulatory GRP receptor and an inhibitory somatostatin type 2 receptor. The D cell has stimulatory CCK, and CCK, receptors and inhibitory muscarinic (either Mj or AA,) receptors. 

Gorelik, J. Zhang, Y Sanchez, D. Shevchuk, A. Frolenkov, G. Klenerman, D. Edwards, C. Korchev, Y, Aldosterone acts via an ATP autocrine/paracrine system The Edelman ATP hypothesis revisited. Proceedings of the National Academy of Sciences of the United States of America 2005,102, 15000-15005. 

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. 

Imura, H and Fukata, J., Endocrine-paracrine interaction in communication between the immune and endocrine systems. Activation of the hypothalamic-pituitary-adrenal axis in inflammation. Eur. J. Endocrinol. 130,32-37 (1994). 

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. 

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. 

The GI system is responsible at its most basic level for providing a continual supply of water, electrolytes, minerals, and nutrients. This is achieved by a myriad of specialized cells and coordinated interplay of motility, secretion, digestion, absorption, blood flow, and lymph flow. These components are under elaborate control of the central and enteric nervous systems, endocrine and paracrine regulation of hormones. The highly complex nature of GI function is clearly illustrated by the estimate that 80 to 100 million neurons exist within the enteric nervous system, a number comparable to that found within the spinal column, hence described as a "second brain."171... 

PTHrP). The receptor signal is mediated by G proteins that activate adenylyl cyclase and the phosphatidylinositol-calcinm second-messenger system. Mntations of PTHRl are associated with abnormalities of development related to altered PTHrP ligand binding. PTHrP is a key paracrine peptide responsible for osteochondrogenesis dnring fetal development (55,56). 

Endocrine and paracrine effects of cytokines and secondary mediators lead to vasodilation and hypotension, hyperactivation of coagulation systems, endothelium damage, increase of leukocyte adhesion as a resnlt of reduced perfusion and hypoxia. 

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. 

Finegold, A.A., Mannes, A.J., ladarola, M.J. A paracrine paradigm for in vivo gene therapy in the central nervous system treatment of chronic pain, Hum. GeneTher. 1999, 10, 1251-1257. 

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