BLOCKADE OF hp-GRF-40-INDUCED GH RELEASE IN NORMAL MEN BY A CHOLINERGIC MUSCARINIC ANTAGONIST

Massara, F; Ghigo, Ezio; Goffi, S.; Molinatti, G. M.; Müller, Eugenio E.; Camanni, F.

doi:10.1210/jcem-59-5-1025

Cited by 88 publications

(40 citation statements)

References 7 publications

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“…Pirenzepine is a mus carinic cholinergic antagonist that blocks the GH response to a variety of stimuli, but not insulin-induced hypoglycaemia [9][10][11]. Our finding of partial blockade of the GH response to GHRH by pirenzepine supports an earlier re port [22], as well as a more recent study by Casanueva et al [5] using atropine. As pirenzepine only poorly penetrates the blood-brain barrier [15], ant there is no evidence for a direct cholinergic modulation of pituitary GH release [3.…”

Section: Discussionsupporting

confidence: 87%

“…Recent studies have demonstrated that the release of serum GH induced by GHRH( I -40) is attenuated by pirenzepine. a cholinergic muscarinic antagonist [22], while proprano lol enhances the rise in serum GH in response to GHRH(I-44)NH; [6]. Shortened analogues of GHRH may also stimulate GH release, and it has been demonstrated that GHRH( I -29) NH: is equipotent to both GHRH( I -40) and GHRH( l-44)NH; on a weight basis [14,21].…”

mentioning

confidence: 99%

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Dopaminergic and Cholinergic Influences on the Growth Hormone Response to Growth Hormone-Releasing Hormone in Man

et al. 1987

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It is well established that compounds that modify dopaminergic and cholinergic activity in man may induce changes in circulating growth hormone (GH). We have, therefore, investigated the effect of a dopamine agonist, bromocriptine, and a dopamine antagonist, domperidone, as well as a muscarinic cholinergic antagonist, pirenzepine, on the GH response to an analogue of GH-releasing hormone (GHRH) in normal male subjects. GHRH(1–29)NH₂ induced a rise in serum GH that was augmented by bromocriptine, antagonized by pirenzepine, but was unaltered by domperidone. As this dose of GHRH(l-29) NH₂ has been shown to be maximally stimulatory to GH release, it is suggested that there are dopamine stimulatory and cholinergic inhibitory receptors to GH release independent of GHRH in man.

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Section: Discussionsupporting

confidence: 87%

mentioning

confidence: 99%

Dopaminergic and Cholinergic Influences on the Growth Hormone Response to Growth Hormone-Releasing Hormone in Man

et al. 1987

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“…Thus, in humans atropine, a muscarinic cholinergic antagonist, or PZ, a more selective antagonist of muscarinic M1 receptors (Watson et al 1983), were able to suppress the GH release elicited by insulin hypoglycemia (Blackard & Waddel 1969), arginine (Casanueva et al 1984) or GHRH (Massara et al 1984), while conversely, pyridostigmine, an acetylcholinesterase (Ach-E) inhibitor, greatly enhanced the GH release elicited by GHRH , Ross et al 1987. Studies in both animals (Torsello et al 1988) and humans (Ross et al 1987) have also disclosed an important cholinergic link in the feedback action of GH, involving SS release.…”

Section: Discussionmentioning

confidence: 99%

Growth hormone responses to growth hormone-releasing hormone and hexarelin in fed and fasted dogs: effect of somatostatin infusion or pretreatment with pirenzepine

Rigamonti¹,

Marazzi²,

Cella³

et al. 1998

Journal of Endocrinology

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Using unanesthetized young male and female beagle dogs, before and after a 2-day fast, we studied the effect of an i.v. infusion of 0·9% saline (5 ml/h), somatostatin (SS, 4 or 8 µg/kg/h) or pretreatment with pirenzepine (PZ, 0·6 mg/kg i.v.), a muscarinic cholinergic antagonist which allegedly releases SS, on the GH release evoked by acute administration of GHRH (2 µg/kg i.v.), hexarelin (HEXA), a member of the GH-releasing peptide family (250 µg/kg i.v.) or GHRH plus HEXA.In fasted dogs, GHRH delivered during saline infusion induced a clear-cut rise in plasma GH levels, significantly higher than that which it induced in fed dogs. In contrast, HEXA, although very effective in causing the release of GH, only slightly increased GH secretion in fasted dogs over that which it induced in fed dogs. Co-administration of GHRH plus HEXA into fed dogs induced a synergic GH response that further increased with fasting.The action of GHRH in fed dogs was abolished by the lower dose of SS, whereas SS at either dose was ineffective in suppressing the GH-releasing effect during fasting. Infusion of the lower dose of SS failed to counter the action of HEXA, either before or during fasting, whilst the higher SS dose partially reduced it in both conditions.In contrast to SS, PZ reduced the GH-releasing effect of GHRH and HEXA, both in the fed state and, though to a lesser extent, during fasting. Pirenzepine only slightly reduced the robust GH rise elicited by GHRH plus HEXA in fed dogs. The suppressive effect of PZ on the GH response to combined administration of the peptides was lowest in fasted dogs.These data show that: (1) fasting augmented the GH response to GHRH and (to a lesser degree) to HEXA; (2) SS inhibited the GH response to GHRH in the fed state, but not in the fasted state; (3) only the higher dose of SS partially reduced the GH stimulation by HEXA in either the fed or the fasted state; (4) PZ lowered the GH response to GHRH and to HEXA in both the fed and (to a lesser degree) the fasted state; (5) PZ did not modify the GH release due to the combined administration of GHRH and HEXA.It is suggested that: (1) during fasting the greatly enhanced GH response to GHRH alone or GHRH plus HEXA probably reflects an augmented GHRH secretion; (2) somatotrope refractoriness to SS may contribute to the enhanced GH secretion in states of calorie deprivation; (3) in contrast to a general belief, muscarinic cholinergic antagonists, e.g. PZ, do not act exclusively via release of SS, but probably also through inhibition of GHRH function.

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“…The selective block of muscarinic receptor blunts the GH release induced by a variety of stimulations [9,11,25,26]. It might be recalled that in another situation, namely anorexia nervosa, pirenzepine fails to antagonize GHRH in the stimulation of GH [27],…”

Section: ]mentioning

confidence: 99%

“…Cholinergic agents or cholinergic tonus enhancement by cholinesterase inhibitors enhance GH serum levels in humans [7,8] and GH response to differ ent stimulatory agents, including GH-releasing hormone (GHRH) [8], Since atropine [9. 10] and pirenzepine [11], but not nicotine [10] block these effects, a muscarinic receptor is thought to be involved.…”

Section: Introductionmentioning

confidence: 99%

Cholinergic Modulation of Growth Hormone-Releasing Hormone Effects on Growth Hormone Secretion in Dementia

et al. 1990

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An impairment of cholinergic and somatostatinergic neurotransmission have been reported in dementia. Both acetylcholine and somatostatin are involved in the regulation of growth hormone (GH) secretion. The effects of GH-releasing hormone (GHRH) 1–44 on GH release have been studied before and after the pretreatment with pyridostigmine or pirenzepine in subjects with senile dementia of the Alzheimer type, multi-infarct dementia and mixed dementia. The data have been compared with those obtained in an age-matched healthy control group. The GH response to GHRH is similar in the patients and in the controls, though the peak occurrence is significantly delayed in dementia. The cholinesterase inhibitor pyridostigmine enhances significantly the GH response to GHRH in both groups. The responses obtained in demented subjects are significantly larger than those found in the controls. Pirenzepine, a muscarinic receptor blocker, inhibits the GHRH effect on GH secretion in both groups. The findings may be interpreted in terms of an underlying impairment of the hypothalamic cholinergic neurotransmission, with an acetylcholine receptor supersensitivity that becomes apparent when the cholinergic tonus is enhanced by the inhibition of cholinesterase by pyridostigmine. No significant differences, due to the type of dementia, have been observed.

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BLOCKADE OF hp-GRF-40-INDUCED GH RELEASE IN NORMAL MEN BY A CHOLINERGIC MUSCARINIC ANTAGONIST

Cited by 88 publications

References 7 publications

Dopaminergic and Cholinergic Influences on the Growth Hormone Response to Growth Hormone-Releasing Hormone in Man

Dopaminergic and Cholinergic Influences on the Growth Hormone Response to Growth Hormone-Releasing Hormone in Man

Growth hormone responses to growth hormone-releasing hormone and hexarelin in fed and fasted dogs: effect of somatostatin infusion or pretreatment with pirenzepine

Cholinergic Modulation of Growth Hormone-Releasing Hormone Effects on Growth Hormone Secretion in Dementia

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