Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute hyperglycemia blocks growth hormone (GH) secretion in response to provocative stimuli including growth hormone releasing hormone (GHRH) administration. However, the precise mechanism of glucose action is unknown. To determine if enhanced somatostatinergic stimulation accounts for the decreased GH secretion, we studied the effect of enhanced cholinergic tone by pyridostigmine on the hyperglycemia blockade of GH release in 7 normal subjects. Pyridostigmine, an acetylcholinesterase inhibitor, has been postulated as an inhibitor of somatostatin release. Each subject underwent 4 tests with GHRH injection (100 micrograms i.v. at 0 min). In the first (control) test, placebo was administered before GHRH. In the second test, 100 g of glucose was administered p.o. 45 min before GHRH. In the third test, pyridostigmine, 120 mg p.o., was administered 60 min before GHRH, and in the fourth test, pyridostigmine, glucose and GHRH were administered at -60, -45 and 0 min, respectively. GHRH-induced GH secretion of 25.8 +/- 4.5 ng/ml was significantly reduced by previous glucose administration (12.1 +/- 4.5 ng/ml) and significantly potentiated by previous pyridostigmine pretreatment (56.5 +/- 16.8 ng/ml). In the fourth test (pyridostigmine plus glucose plus GHRH) the GH peak of 42.4 +/- 9.2 ng/ml was significantly higher than after GHRH alone and not different to the pyridostigmine-GHRH test. In conclusion, central cholinergic activation by pyridostigmine reversed the hyperglycemic blockade of GHRH-induced GH secretion. In addition, hyperglycemia was unable to reduce the potentiating effect of pyridostigmine on GH secretion elicited by GHRH. Based on the reported actions of pyridostigmine, acute hyperglycemia might act over GH release by inducing hypothalamic somatostatin release.
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PMID:Activation of cholinergic neurotransmission by pyridostigmine reverses the inhibitory effect of hyperglycemia on growth hormone (GH) releasing hormone-induced GH secretion in man: does acute hyperglycemia act through hypothalamic release of somatostatin? 256 42

Pirenzepine, a muscarinic antagonist probably acting via stimulation of hypothalamic somatostatin release, abolishes the growth hormone releasing hormone (GHRH)-stimulated growth hormone (GH) rise in normal subjects but only blunts it in patients with anorexia nervosa (AN). This finding suggested the existence in AN of an alteration of cholinergic system and/or somatostatinergic tone. To further investigate these mechanisms, in 11 AN women patients (age 18.8 +/- 0.9 years; BMI 13.4 +/- 0.4) we studied the GH response alone (1 microgram/Kg IV as a bolus at 0 min) and combined with pyridostigmine (PD, 120 mg orally, 60 min before GHRH administration), a cholinesterase inhibitor, or arginine (ARG 30 g infused over 30 min starting at 0 min), two compounds probably acting via inhibition of hypothalamic somatostatin (SS) release. The GH response to GHRH preceded by a previous (120 min before) neurohormone administration also was studied. All these tests also were performed in 20 normal age-matched women (age 22.0 +/- 1.8 yrs; BMI20.1 +/- 2.4). Basal serum GH levels were higher in AN patients than in normal volunteers (NV) (10.3 +/- 3.4 versus 2.8 +/- 0.3 microgram/L; p < 0.001), whereas plasma IGF-I levels were lower in AN patients than in NV (43.3 +/- 10.6 versus 172.4 +/- 13.9 micrograms/L; p < 0.00001). In AN patients, GHRH administration induced a GH rise higher, though not significantly, than that in NV [delta area under the curve (AUC) 1173.6 +/- 167.6 versus 834.6 +/- 188.1 micrograms/L/h]. The GH response to the second of two consecutive GHRH boluses was lower (p < 0.01) than that of the first one either in AN patients or in NV (67.6 +/- 27.4 and 53.1 +/- 25.7 micrograms/L/h, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arginine but not pyridostigmine, a cholinesterase inhibitor, enhances the GHRH-induced GH rise in patients with anorexia nervosa. 788 Sep 38