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)

Previous work has shown that growth hormone-releasing factor (GRF) stimulates cGMP production and somatostatin [somatotropin (growth hormone)-release-inhibiting factor, SRIF] release without altering cAMP accumulation by fragments of median eminence incubated in vitro. Therefore, this study was undertaken to evaluate the effect of GRF and cGMP on SRIF mRNA and SRIF release in the periventricular nuclei of male rats in vitro. SRIF mRNA levels were determined in explants of periventricular nuclei incubated for 6 hr in Waymouth's medium in the presence of various substances. Steady-state levels of SRIF mRNA were measured by an S1 nuclease protection assay using a 32P-labeled rat SRIF RNA probe. SRIF release and cGMP formation were measured at 30 min and 6 hr by RIA. SRIF mRNA levels and SRIF release were significantly (P < 0.025) increased (approximately 2-fold) by 1 microM dibutyryl cGMP, whereas sodium butyrate had no effect. This augmentation was not influenced by cycloheximide, an inhibitor of protein synthesis. Sodium nitroprusside (10 microM), an activator of the guanylate cyclase pathway via its release of nitric oxide, augmented (P < 0.001) SRIF mRNA levels and significantly increased (P < 0.05) SRIF release. GRF (1 nM) increased SRIF mRNA (P < 0.001) and stimulated the release of SRIF at 30 min (P < 0.05) and 6 hr (P < 0.01). This stimulation was abolished by 10 microM NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthase, but not by NG-monomethyl-D-arginine (D-NMMA, the inactive isomer). GRF also increased cGMP formation. This effect was completely blocked by incubation with L-NMMA but not D-NMMA. These results indicate that GRF releases nitric oxide. The nitric oxide diffuses to the adjacent SRIF neurons, where it activates guanylate cyclase, leading to increased formation of cGMP. This cGMP increases SRIF mRNA and SRIF release in the periventricular nuclei of male rats.
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PMID:Growth hormone-releasing factor increases somatostatin release and mRNA levels in the rat periventricular nucleus via nitric oxide by activation of guanylate cyclase. 790 58

Ghrelin, a recently discovered 28-aa peptide, stimulates GH release through a mechanism involving PLC- and cAMP-related signaling pathways. Recently, nitric oxide (NO) and its mediator, cGMP, have been shown to be required for the response of somatotropes to various regulators (GHRH, somatostatin, leptin). Here, we explore the possible role of the NO synthase (NOS)/NO/guanylate cyclase (GC)/cGMP signaling pathway in ghrelin-induced GH release from cultured pig somatotropes using blockers or activators of this route.
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PMID:Ghrelin induces growth hormone (GH) secretion via nitric oxide (NO)/cGMP signaling. 1589 Oct 86

There is increasing evidence that nitric oxide (NO) produced by NO synthase (NOS), and their signalling partners, guanylyl cyclase and cGMP, play a relevant role in growth hormone (GH) secretion from somatotrophs. We previously demonstrated that both GH-releasing hormone (GHRH; 10(-8) M) and low concentrations of somatostatin (10(-15) M) stimulate pig GH release in vitro, whereas a high somatostatin concentration (10(-7) M) inhibits GHRH-induced GH secretion. To ascertain the possible contribution of the NOS-NO and guanylyl cyclase-cGMP routes to these responses, cultures of pituitary cells from prepubertal female pigs were treated (30 min) with GHRH (10(-8) M) or somatostatin (10(-7) or 10(-15) M) in the absence or presence of activators or blockers of key steps of these signalling cascades, and GH release was measured. Two distinct activators of NO route, SNAP (5x10(-4) M) or L-AME (10(-3) M), similarly stimulated GH release when applied alone (with this effect being blocked by 10(-7) M somatostatin), but did not alter the stimulatory effect of GHRH or 10(-15) M somatostatin. Conversely, two NO pathway inhibitors, NAME (10(-5) M) or haemoglobin (20 microg/ml) similarly blocked GHRH- or 10(-15) M somatostatin-stimulated GH release. 8-Br-cGMP (10(-8) to 10(-4) M) strongly stimulated GH release, suggesting that cGMP may function as a subsequent step in the NO pathway in this system. Interestingly, 10(-7) M somatostatin did not inhibit the stimulatory effect of 8-Br-cGMP. Moreover, although 8-Br-cGMP did not modify the effect of GHRH, it enhanced GH release stimulated by 10(-15) M somatostatin. Accordingly, a specific guanylyl cyclase inhibitor, LY-83, 583 (10(-5) M) did not alter 10(-15) M somatostatin-induced GH release, whereas it blocked GHRH-induced GH secretion. These results demonstrate for the first time that the NOS/NO signalling pathway contributes critically to the stimulatory effects of both GHRH and low-concentration somatostatin on GH release, and that, conversely, the subsequent guanylyl cyclase/cGMP step only mediates GHRH- and not low-concentration somatostatin-induced GH secretion from somatotrophs.
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PMID:Differential contribution of nitric oxide and cGMP to the stimulatory effects of growth hormone-releasing hormone and low-concentration somatostatin on growth hormone release from somatotrophs. 1610 96