Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tritium-labeled synthetic fragments of human adrenocorticotropic hormone (ACTH) [3H]ACTH (11-24) and [3H]ACTH (15-18) with a specific activity of 22 and 26 Ci/mmol, respectively, were obtained. It was found that [3H]ACTH (11-24) binds to membranes of the rat adrenal cortex with high affinity and high specificity (Kd 1.8 +/- 0.1 nM). Twenty nine fragments of ACTH (11-24) were synthesized, and their ability to inhibit the specific binding of [3H]ACTH (11-24) to adrenocortical membranes was investigated. The shortest active peptide was found to be an ACTH fragment (15-18) (KKRR) (Ki 2.3 +/- 0.2 nM), whose [3H] labeled derivative binds to rat adrenocortical membranes (Kd 2.1 +/- 0.1 nM) with a high affinity. The specific binding of [3H]ACTH-(15-18) was inhibited by 100% by unlabeled ACTH (11-24) (Ki 2.0 +/- 0.1 nM). ACTH (15-18) in the concentration range of 1-1000 nM did not affect the adenylate cyclase activity of adrenocortical membranes and, therefore, is an antagonist of the ACTH receptor.
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PMID:[Synthetic peptide KKRR corresponding to the human ACTH fragment 15-18 is an antagonist of the ACTH receptor]. 1836 34

The hypothalamic-pituitary-adrenal (HPA) axis is activated under various stressors. Corticotropin-releasing factor (CRF) plays a central role in controlling stress response, and regulating the HPA axis. CRF, produced in the hypothalamic paraventricular nucleus (PVN), stimulates adrenocorticotropic hormone (ACTH) production via CRF receptor type 1 (CRF(1) receptor) from the corticotrophs of the anterior pituitary (AP). Cyclic AMP (cAMP)-protein kinase A (PKA) pathway takes a main role in stimulating CRF gene transcription. Forskolin and pituitary adenylate cyclase-activating polypeptide (PACAP) stimulate adenylate cyclase, intracellular cAMP production, and then CRF and arginine vasopressin (AVP) gene expression in hypothalamic 4B cells. Interleukin (IL)-6, produced in the PVN, both directly and indirectly stimulates CRF and AVP gene expression. Estradiol may enhance the activation of CRF gene expression in response to stress. The HPA axis is regulated by a negative feedback mechanism, because glucocorticoids inhibit both CRF production in the hypothalamic PVN and ACTH production in the pituitary. Hypothalamic parvocellular neurons in the PVN are known to express glucocorticoid receptors, and glucocorticoids are able to regulate CRF gene transcription and expression levels directly in the PVN. Glucocorticoids-dependent repression of cAMP-stimulated CRF promoter activity is mainly localized to promoter sequences between -278 and -233 bp. Both negative glucocorticoid regulatory element (nGRE) and serum response element (SRE) are involved in the repression of the CRF gene in the hypothalamic cells.
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PMID:Regulatory mechanisms underlying corticotropin-releasing factor gene expression in the hypothalamus. 1935 56

The major endocrine response to stress occurs via activation of the hypothalamic-pituitary-adrenal (HPA) axis, leading ultimately to increases in circulating glucocorticoids, which are essential for the metabolic adaptation to stress. The major players in the HPA axis are the hypothalamic neuropeptide, corticotropin releasing hormone (CRH), the pituitary hormone adrenocorticotropic hormone, and the negative feedback effects of adrenal glucocorticoids. In addition, a number of other neuropeptides, including vasopressin (VP), angiotensin II, oxytocin, pituitary adenylate cyclase activating peptide, orexin and cholecystokinin, and nesfatin can affect HPA axis activity by influencing the expression and secretion of CRH, and also by modulating pituitary corticotroph function or adrenal steroidogenesis. Of these peptides, VP co-secreted with CRH from axonal terminals in the external zone of the median eminence plays a prominent role by potentiating the stimulatory effect of CRH and by increasing the number of pituitary corticotrophs during chronic challenge. Although the precise role and significance of many of these neuropeptides in regulating HPA axis activity requires further investigation, it is likely that they are part of a multifactorial system mediating the fine tuning of HPA axis activity during adaptation to a variety of physiological and stressful conditions.
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PMID:Regulation of the hypothalamic-pituitary-adrenal axis by neuropeptides. 2596 Dec 71


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