INT136415

Context Info Confidence 0.70 First Reported 2006 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 6 Total Number 10 Disease Relevance 3.83 Pain Relevance 0.49

Anatomy Link Frequency MC3 1 GHS (Homo sapiens)

Pain Link Frequency Relevance Heat antagonist 98 99.80 monoamine 1 99.44 Somatostatin 50 99.36 Cannabinoid 11 98.72 Serotonin 1 98.36 Cholecystokinin 6 61.60 Neuropeptide 17 55.52 Opioid 1 51.76 Pain 6 50.00 Inflammation 50 16.48

Disease Link Frequency Relevance Heat Obesity 81 99.84 Chronic Disease 5 99.70 Aging 114 99.00 Frailty 27 97.36 Weight Gain 18 95.44 Appetite Loss 71 93.96 Shoulder Pain 1 90.76 Body Weight 24 90.60 Shoulder Dislocation 3 90.00 Insulin Resistance 28 89.96

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

A sample of 107 hemiplegic adults with recent stroke (less than 30 days from onset) was differentiated into two groups according to the presence of GHS.

Localization (presence) of GHS

1) Confidence 0.70 Published 2007 Journal Physiother Res Int Section Body Doc Link 17536647 Disease Relevance 0.18 Pain Relevance 0

The last observation is significant, because higher doses of ghrelin/GHS evoke ACTH, cortisol, and prolactin secretion acutely in humans and animals, putatively by inducing hypothalamic secretion of one or both primary ACTH-releasing peptides, corticotrophin-releasing hormone (CRH), and arginine vasopressin (AVP) [272, 274–278].

Localization (secretion) of GHS

2) Confidence 0.31 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.21 Pain Relevance 0.03

Whereas both glucocorticoid deficiency and excess in chronic diseases can reduce GH response to GHS [4, 421], combined GHRH and ghrelin infusion is more effective at driving GH secretion than ghrelin alone [270]: Figure 8.

Localization (response) of GHS associated with chronic disease

3) Confidence 0.29 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.83 Pain Relevance 0

Congeneric molecules include GHRP-2, GHRP-6, hexarelin, ipamorelin, ibutamorelin, and the nonpeptide MK-0677, which like ghrelin rapidly induce inositol triphosphate, diacylglycerol, and Ca2+ release via the GHS-R1a [51, 63–67]. 2.4.

Localization (release) of GHS

4) Confidence 0.29 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.42 Pain Relevance 0

Since highly selective GHS-R1a antagonists are not available for clinical investigation, determining the exact extent to which endogenous ghrelin participates in amplifying GH secretion in human physiology, including in utero, in infancy, childhood, puberty, adulthood, and senescence remains difficult [4, 65, 250].

Localization (selective) of GHS associated with aging and antagonist

5) Confidence 0.29 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.16 Pain Relevance 0.05

Likewise, why age and obesity impair GHS-induced secretion of GH but not of ACTH and prolactin is not known [113, 281].

Localization (secretion) of GHS associated with obesity

6) Confidence 0.24 Published 2010 Journal International Journal of Peptides Section Body Doc Link PMC2925380 Disease Relevance 0.21 Pain Relevance 0

Replacement of GH or stimulation of GH secretion with GH-releasing hormone (GHRH) or other GH secretagogues (GHS) would thus seem to be an appealing option to delay the onset of frailty in older adults and to prolong the capacity for independent living; but the balance of pros and cons is not necessarily the same as in AGHD.

Localization (secretagogues) of GHS associated with frailty

7) Confidence 0.11 Published 2008 Journal Clinical Interventions in Aging Section Body Doc Link PMC2544358 Disease Relevance 0.47 Pain Relevance 0

This review describes the components of the GH axis and their actions, compares and contrasts normal aging with AGHD; and summarizes GH replacement and the use of GHRH and GHS in these contexts.

Localization (use) of GHS associated with aging

8) Confidence 0.11 Published 2008 Journal Clinical Interventions in Aging Section Body Doc Link PMC2544358 Disease Relevance 0.43 Pain Relevance 0.03

Additionally, there are other substances which can enhance GH response to GHS by suppressing somatostatin secretion, including arginine and beta-adrenergic antagonists, which could potentially enhance treatment effects (Merriam et al 1997).

Localization (response) of GHS associated with antagonist and somatostatin

9) Confidence 0.11 Published 2008 Journal Clinical Interventions in Aging Section Body Doc Link PMC2544358 Disease Relevance 0.60 Pain Relevance 0.10

In six reviews, the melanocortins system (including MC4 and MC3 receptors, Agrp, MSH), the NPY receptors (including NPY-Y1, NPY-Y2, and NPY-Y5, PYY3-36), the cannabinoid system (including the development of rimonabant), the ghrelin (GHS, growth hormone secretagogue) system, the monoamine GPCRs (including serotonin, adrenergic and histamine receptors), orexin (hypocretin) system and the galanin receptors are covered.

Localization (secretagogue) of GHS in MC3 associated with cannabinoid, serotonin and monoamine

10) Confidence 0.06 Published 2006 Journal CNS Neurol Disord Drug Targets Section Abstract Doc Link 16787226 Disease Relevance 0.32 Pain Relevance 0.29

General Comments

This test has worked.