Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously we reported that intracerebroventricular (i.c.v.) administration of nitric oxide (NO) donors, sodium nitroprusside (SNP) (1-10 microg), and 3-morpholino-sydnonimine (SIN-1) (10-100 microg), induced dose-dependent increases in plasma prolactin levels of freely moving male rats, suggesting a role of NO in the control of prolactin secretion. The present results show that i.c.v. pretreatment with methylene blue (MB) (30 microg), a guanylyl cyclase inhibitor, significantly reduced the effects of microinjections of SNP (3 and 5 microg), however, this did not modify the stimulatory action of SIN-1 (30 microg) on plasma prolactin levels of conscious male rats. Alone, MB did not modify basal prolactin levels. These results suggest different mechanisms of action of SNP and SIN-1 to stimulate prolactin secretion in vivo. Activation of soluble guanylyl cyclase seems to mediate the neuroendocrine action of NO released from SNP but not of SIN-1. Different cellular distribution of NO generating activity from these donors as well as the possible generation of other radicals simultaneously with NO from SIN-1 could explain these differences.
 ...
PMID:Methylene blue inhibits stimulatory effect of sodium nitroprusside but not of 3-morpholino sydnonimine on prolactin secretion in freely moving male rats. 966 16

Nitric oxide (NO), generated by endothelial (e) NO synthase (NOS) and neuronal (n) NOS, plays a ubiquitous role in the body in controlling the function of almost every, if not every, organ system. Bacterial and viral products, such as bacterial lipopolysaccharide (LPS), induce inducible (i) NOS synthesis that produces massive amounts of NO toxic to the invading viruses and bacteria, but also host cells by inactivation of enzymes leading to cell death. The actions of all forms of NOS are mediated not only by the free radical oxidant properties of this soluble gas, but also by its activation of guanylate cyclase (GC), leading to the production of cyclic guanosine monophosphate (cGMP) that mediates many of its physiological actions. In addition, NO activates cyclooxygenase and lipoxygenase, leading to the production of physiologically relevant quantities of prostaglandin E2 (PGE2) and leukotrienes. In the case of iNOS, the massive release of NO, PGE2, and leukotrienes produces toxic effects. Systemic injection of LPS causes induction of interleukin (IL)-1 beta mRNA followed by IL-beta synthesis that induces iNOS mRNA with a latency of two and four hours, respectively, in the anterior pituitary and pineal glands, meninges, and choroid plexus, regions outside the blood-brain barrier, and shortly thereafter, in hypothalamic regions, such as the temperature-regulating centers, paraventricular nucleus containing releasing and inhibiting hormone neurons, and the arcuate nucleus, a region containing these neurons and axons bound for the median eminence. We are currently determining if LPS similarly activates cytokine and iNOS production in the cardiovascular system and the gonads. Our hypothesis is that recurrent infections over the life span play a significant role in producing aging changes in all systems outside the blood-brain barrier via release of toxic quantities of NO. NO may be a major factor in the development of coronary heart disease (CHD). Considerable evidence has accrued indicating a role for infections in the induction of CHD and, indeed, patients treated with a tetracycline derivative had 10 times less complications of CHD than their controls. Stress, inflammation, and infection have all been shown to cause induction of iNOS in rats, and it is likely that this triad of events is very important in progression of coronary arteriosclerosis leading to coronary occlusion. Aging of the anterior pituitary and pineal with resultant decreased secretion of pituitary hormones and the pineal hormone, melatonin, respectively, may be caused by NO. The induction of iNOS in the temperature-regulating centers by infections may cause the decreased febrile response in the aged by loss of thermosensitive neurons. iNOS induction in the paraventricular nucleus may cause the decreased nocturnal secretion of growth hormone (GH) and prolactin that occurs with age, and its induction in the arcuate nucleus may destroy luteinizing hormone-releasing hormone (LHRH) neurons, thereby leading to decreased release of gonadotropins. Recurrent infections may play a role in aging of other parts of the brain, because there are increased numbers of astrocytes expressing IL-1 beta throughout the brain in aged patients. IL-1 and products of NO activity accumulate around the plaques of Alzheimer's, and may play a role in the progression of the disease. Early onset Parkinsonism following flu encephalitis during World War I was possibly due to induction of iNOS in cells adjacent to substantia nigra dopaminergic neurons leading to death of these cells, which, coupled with ordinary aging fall out, led to Parkinsonism. The central nervous system (CNS) pathology in AIDS patients bears striking resemblance to aging changes, and may also be largely caused by the action of iNOS. Antioxidants, such as melatonin, vitamin C, and vitamin E, probably play an important acute and chronic role in reducing or eliminating the oxidant damage produced by NO.
 ...
PMID:The nitric oxide hypothesis of aging. 995 25

Nitric oxide (NO), a highly reactive free radical, has been identified as a neurotransmitter in the central and peripheral nervous system. NO synthase (NOS) is the enzyme responsible for NO production from L-arginine and plays an important role in regulating the release of several hypothalamic peptides. In the pituitary, NO was found to increase growth hormone (GH) secretion in several in vitro and in vivomodels. However, its role in human GH regulation is unknown. The aim of this study was to investigate the regulatory effects of NO on human GH and prolactin secretion using primary cell cultures of human fetal pituitaries and cultured hormone-secreting adenomas. Incubation of the human fetal pituitaries (21-24 wk gestation) in the presence of sodium nitroprusside (SNP; 1 mM), a NO donor, for 4 h resulted in a 50-75% increase in GH secretion, similar to the stimulatory effect evoked by growth hormone-releasing hormone (GHRH) (10 nM). However, fetal PRL secretion was not affected by SNP. GH release was also stimulated (40-70% increase) by SNP in 60% of the cultured GH-secreting adenomas studied. SNP-induced GH release was inhibited in both fetal and adenomatous cells by PTI0, a NO scavenger. The addition of cGMP (0.1-1 mM), the second messenger of multiple NO actions, enhanced fetal and adenomatous GH secretion by 55-95%. Neuronal NOS (nNOS) was expressed in normal (fetal and adult) human pituitary tissues and in GH-secreting adenomas. Examination of its functional expression using L-arginine (1 microM) yielded a 35% increase in GH release from cultured GH-secreting adenoma. This response was blocked by a NOS inhibitor with high selectivity for the neuronal enzyme and by a guanylyl cyclase inhibitor. In conclusion, NO stimulates human GH in cultured fetal pituitaries and GH-secreting adenomas. Cyclic GMP is probably involved in this hormonal regulation.
 ...
PMID:Nitric oxide stimulates growth hormone secretion from human fetal pituitaries and cultured pituitary adenomas. 1638 95

C-type natriuretic peptide (CNP) cDNA was cloned from the tilapia brain and its inferred mature sequence was chemically synthesized together with previously cloned tilapia A-type and B-type natriuretic peptides (ANP and BNP). The cloned CNP belongs to the CNP-1 type of teleosts. Reverse-transcription polymerase chain reaction showed that the ANP and BNP genes were hardly expressed in the tilapia brain and pituitary, whereas the CNP gene was expressed strongly in the brain and slightly in the pituitary. Effects of homologous natriuretic peptides (100 nM each) on growth hormone (GH) and prolactin (PRL) release were examined using dispersed tilapia pituitary cells. Tilapia ANP and BNP stimulated GH and PRL release during 4-8, and 8-24 h of incubation. BNP appeared to be more potent than ANP, also stimulating GH and PRL release during 0-4 h of incubation. CNP stimulated GH release only during 4-8 h of incubation; CNP was without effect on PRL release. All three NPs stimulated GH and PRL mRNA expression in dispersed pituitary cells following 24 h of incubation. ANP and BNP significantly elevated intracellular cGMP accumulation in dispersed pituitary cells after 15 min of exposure, whereas no effect of CNP was observed. These results indicate a long-lasting stimulation of GH and PRL release by ANP and BNP that is mediated, at least in part, by the guanylyl cyclase-linked NP receptor.
 ...
PMID:In vitro effects of homologous natriuretic peptides on growth hormone and prolactin release in the tilapia, Oreochromis mossambicus. 1710 75


<< Previous 1 2