Paracrine

Transport in the blood is no longer a requisite for a hormonal response. Responses can occur after release of hormones into the interstitial fluid with binding to receptors in nearby ceUs, called paracrine control, or binding to receptors on the ceU that released the hormone, called autocrine control. A class of hormones shown to be synthesized by the tissue in which they act or to act in the local ceUular environment are the prostaglandins (qv). These ubiquitous compounds are derived from arachidonic acid [506-32-1] which is stored in the ceU membranes as part of phosphoHpids. Prostaglandins bind to specific ceUular receptors and act as important modulators of ceU activity in many tissues. 

Nontraditional Hormones. Novel hormones identified ia cardiovascular tissue have profound effects on maintenance of blood pressure and blood volume ia mammals. Atrial natriuretic hormone (ANH) is a polypeptide hormone secreted from the atria of the heart. When the cardiac atrium is stretched by increased blood volume, secretion of ANH is stimulated ANH ia turn increases salt and water excretion and reduces blood pressure (6). Endothelin is a polypeptide hormone secreted by endothehal cells throughout the vasculature. Although endothelin is released into the circulation, it acts locally in a paracrine fashion to constrict adjacent vascular smooth muscle and increase blood pressure (7). 

P and Pg, exist in foUicular fluid. Control of inhibin secretion involves a feedback relationship in which circulating FSH stimulates inhibin secretion, which in turn reduces the secretion of FSH (8). Both the homo- and the heterodimers of the P-subunits of inhibin promote the secretion of FSH and thus have been termed activins. Activin is secreted by the ovary and the testes into the circulation. In addition, both inhibin and activin have intragonadal autocrine and paracrine effects that influence gonadal steroidogenesis (9). 

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. 

Natural or synthethic receptor ligands that induce a conformational change (active conformation) and a signal transduction process upon receptor binding. Agonists may act as typical hormones or neurotransmitters or they may confer paracrine functions, recognize bacterial, viral or other environmental constituents via activating their dedicated receptors. 

In malignant prostate epithelial cells, auto- and paracrine release of ET-1 is a critical factor in ETA receptor-mediated proliferation [5]. In addition, the ET-1/ETa receptor axis has emerged as a potential target in prostate cancer bone metastasis... 

Natriuretic peptides are a family of peptide hormones. All of them contain a 17-amino acid long ring that is closed by a disulfide bond between two cysteine residues. ANP (atrial natriuretic peptide) is mainly expressed in the atria of the heart, whereas BNP (B-type natriuretic peptide) is synthesized in the ventricular myocardium. CNP occurs mainly in the endothelium and is thought to have a paracrine function. ANF and BNF lower blood pressure by a direct effect on smooth muscle and on the salt retention in the kidney. Natriuretic peptides bind and activate particulate guanylyl cyclases. 

Extrahypothalamic OX-B-like immunoreactivity, reminiscent to that of CRF, has been described in clustered GABAergic neuronal populations, in the lateral division of central nucleus ofthe amygdala, the bednucleus of the stria terminalis, and in the hippocampus. Moreover, ectopic expression of preproorexin mRNA in the gut, ependymal cells, neuroblastomas, and of orexin receptors in adrenal gland, cancer and hematopietic stem cells suggests yet unexplored roles of orexins as paracrine factors controlling blood-brain barrier, and tumor or stem cell function. 

PGs act locally in an autocrine or paracrine fashion in the tissues in which they are synthesized, rather than as circulating hormones, which act at a distant site. For this reason, studies localizing the enzymatic machinery, which synthesize prostaglandins, are informative with respect to the site of PG actions. PG synthesis is... 

Somatostatin acts on various organs, tissues and cells as neurotransmitter, paracrine/autocrine and endocrine regulator on cell secretion, smooth muscle contractility, nutrient absorption, cell growth and neurotransmission [1]. Some of its mainly inhibitory effects are listed in Table 1. Somatostatin mediates its function via a family of heptahelical G-protein-coupled receptors termed... 

In addition, several other organs, like the heart, ovaty, amnion, chorion, decidua, testis, epididymis and prostate, have been reported to synthesize OT, suggesting a paracrine role for this hormone in these tissues. Ectopic AVP production by lung cancer cells or other neoplasms has been described in humans, leading to the syndrome of inappropriate antidiuretic hormone secretion. 

OTRs are mainly expressed in myoepithelial cells of the galactiferus channels and the myometrium. The OTRs in vascular endothelial cells, renal epithelial cells (macula densa, proximal tubule) and cardiomyocytes induce the production of NO (vasodilation), natriuresis and release of ANP, respectively. The endometrium, ovary, amnion, testis, epididymis, prostate and thymus also express the OTR supporting a paracrine role of this peptide. Osteoblasts, osteoclasts, pancreatic islets cells, adipocytes, and several types of cancer cells also express OTRs. More over, expression of the OTR... 

Figure 1. Autocrine and paracrine factors. Many animal cells secrete regulatory factors called autocrine factors, which then interact with specific receptors on the surface of the same cells, so as to modulate cell function. Animal cells may also secrete regulatory factors called paracrine factors, which interact with specific receptors on different cells in the same locale, modulating their functional properties.

TGFs are secreted by animal cells following their biosynthesis. Subsequently, these TGFs may either stimulate the growth of the very cells that have produced them (in this case, the TGFs act as autocrine factors), or may stimulate the growth of other adjacent cell types (in this case, the TGFs act as paracrine factors). 

Fig. 4.4 Simplified hypothesis of the mechanism of gpI20-induced dorsal root gangUon (DRG) neurotoxicity. CXCR4 binding on Schwann cells by SDF-Ia or gpI20 results in the release of RANTES, which induces tumor necrosis factor (TNF)-a production by DRG neurons, and subsequent TNFRl-mediated neurotoxicity in an autocrine/paracrine fashion. Reproduced with permission of John Wiley Sons, Inc. (Keswani et al. 2003b)...

Knapp PE, Itkis OS, Zhang L, Spruce BA, BakaUdn G, Hauser KF (2001) Endogenous opioids and oligodendroglial function possible autocrine/paracrine effects on cell survival and development. Glia 35 156-165... 

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