Effect of Δ9- and Δ8-Tetrahydrocannabinol on the Peripheral Autonomic Nervous System In Vitro

1973 ◽  
Vol 51 (1) ◽  
pp. 12-21 ◽  
Author(s):  
A. L. Gascon ◽  
M. T. Pérès

The purpose of this study was to evaluate the effect of Δ9- and Δ8tetrahydrocannabinol (THC) on some isolated muscles. The results observed show that Δ9- and Δ8THC do not have agonistic activity on the vas deferens, the phrenic nerve – diaphragm, and the ileum preparations. On the other hand, both compounds produce a transient potentiation followed by the inhibition of the acetylcholine-induced contraction as well as a potentiation of the musculotropic activity of noradrenaline on the isolated vas deferens. Furthermore, we have observed that Δ8THC reverses the anti-cholinergic action of atropine, conteracts the anti-angiotensin activity of morphine, and finally, abolishes the potentiation of noradrenaline produced by cocaine. On the phrenic nerve – diaphragm preparation Δ9THC does not modify the contraction produced by nerve stimulation but alters the effect of physostigmine, an anti-cholinesterase inhibitor.

2019 ◽  
Author(s):  
Ana M. Cruz ◽  
Yasaman Malekizadeh ◽  
Julia M. Vlachaki Walker ◽  
Paul G. Weightman Potter ◽  
Katherine Pye ◽  
...  

ABSTRACTAMP-activated protein kinase (AMPK) is a critical cellular and whole body energy sensor activated by energy stress, including hypoglycemia, which is frequently experienced by people with diabetes. Previous studies using direct delivery of an AMPK activator to the ventromedial hypothalamus (VMH) in rodents increased hepatic glucose production. Moreover, recurrent glucoprivation in the hypothalamus leads to blunted AMPK activation and defective hormonal responses to subsequent hypoglycemia. These data suggest that amplifying AMPK activation may prevent or reduce frequency hypoglycemia in diabetes. We used a novel brain-permeable AMPK activator, R481, which potently increased AMPK phosphorylation in vitro. R481 significantly increased peak glucose levels during glucose tolerance tests in rats, which were attenuated by treatment with AMPK inhibitor SBI-0206965 and completely abolished by blockade of the autonomic nervous system. This occurred without altering insulin sensitivity measured by hyperinsulinemic-euglycemic clamps. Endogenous insulin secretion was not altered by R481 treatment. During hyperinsulinemic-hypoglycemic clamp studies, R481 treatment reduced exogenous glucose requirements and amplified peak glucagon levels during hypoglycemia. These data demonstrate that peripheral administration of the brain permeable AMPK activator R481 amplifies the counterregulatory response to hypoglycemia in rats, which could have clinical relevance for prevention of hypoglycemia.


1983 ◽  
Vol 3 (4) ◽  
pp. 319-330 ◽  
Author(s):  
Jan M. Kitzen ◽  
Mary A. Schwenkler ◽  
Janice E. Moeller ◽  
Luther D. Hellyer ◽  
Sandy J. Wilson

Author(s):  
J. Z. Young

There are not sufficient data available to allow any general statements about the earlier stages of evolution of the autonomic nervous system and of its various transmitter mechanisms. In the previous paper (Young, 1980) it was shown that control of the stomach of elasmobranchs is largely by the inhibitory action of the sympathetic nerves, probably mediated by 5-HT. In teleostean fishes on the other hand control seems to be mainly by the cholinergic excitatory action of the vagus, especially in the more advanced (acanthopterygian) groups (Grove & Campbell, 1979a, b; Fänge & Grove, 1979).


2007 ◽  
Vol 292 (4) ◽  
pp. E1069-E1078 ◽  
Author(s):  
Paul Mitrani ◽  
Malathi Srinivasan ◽  
Catherine Dodds ◽  
Mulchand S. Patel

An early dietary intervention in the form of a high-carbohydrate (HC) milk formula in neonatal rat pups results in immediate onset of hyperinsulinemia. While increased insulin secretion in HC rats has been shown to be related to hypersensitivity to glucose, the immediate onset of hyperinsulinemia and its persistence throughout the suckling period suggest involvement of multiple systems that enhance insulin secretion in response to increased demand. Evidence presented here in 12-day-old HC rats indicates that altered activity of the autonomic nervous system contributes to enhanced insulin secretory responses to glucose stimulation through increased parasympathetic and decreased sympathetic signaling. Both in vivo and in vitro studies have shown that HC rats secrete significantly higher levels of insulin in response to glucose in the presence of acetylcholine, a cholinergic agonist, while sensitivity to inhibition of insulin secretion by oxymetazoline, an α2a-adrenergic receptor (α2aAR) agonist, was reduced. In addition, HC rats showed increased sensitivity to blockade of cholinergic-induced insulin secretion by the muscarinic type 3 receptor (M3R) antagonist 4-diphenylacetoxy- N-methylpiperidine methobromide, as well as increased potentiation of glucose-stimulated insulin secretion by treatment with yohimbine. Increases in islets levels of M3R, phospholipase C-β1, and protein kinase Cα mRNAs, as well as decreased α2aAR mRNA, in 12-day-old HC rats provide a mechanistic connection to the changes in insulin secretion seen in HC rats. In conclusion, altered autonomic regulation of insulin secretion, due to the HC nutritional intervention, contributes to the development of hyperinsulinemia in 12-day-old HC rats.


Author(s):  
O. Zhurenko ◽  
◽  
V. Karpovskyi ◽  
V. Zhurenko ◽  
◽  
...  

The tone of the autonomic nervous system is considered on the one hand as one of the manifestations of homeostasis, and on the other hand, as one of the mechanisms of its regulation. The predominance of the tonic effect of the parasympathetic and sympathetic departments of the autonomic nervous system is defined as vagotonia and sympathicotonia. The tone of the autonomic nervous system in cows was determined using a trigeminal vagal test. According to the results, the animal was classified as normotonic, sympathicotonic or vagotonic. The tone of the autonomic nervous system in cows in summer inversely correlated with copper content in whole blood (r=-0.62; p<0.05) and blood cells (r=-0.58; p<0.05). In winter, the correlation of the tone of the autonomic nervous system in cows with its content in whole blood, serum and blood cells did not reach significant values (r=-0.21–0.36). Increased tone of the parasympathetic department of the autonomic nervous system, regardless of the season, had almost no effect on copper content in serum, whole blood and its cells (ղ²x=0.01–0.23). At the same time, sympathicotonia in summer has a significant impact only on the copper content in blood cells – ղ²x=0.58 (p<0.05), while in winter this effect increased significantly (ղ²x=0.91; p<0.001). The multifactor analysis of variance revealed the dependence of copper content on the tone of the autonomic nervous system and the season. However, the vegetative status of cows had a significant impact on its content only in blood cells (F=8.59>FU=4.41; p<0.01), and the season limited copper content only in whole blood (F=12.12>FU=3.55; p<0.01).


2021 ◽  
Vol 12 ◽  
Author(s):  
Ana M. Cruz ◽  
Katie M. Partridge ◽  
Yasaman Malekizadeh ◽  
Julia M. Vlachaki Walker ◽  
Paul G. Weightman Potter ◽  
...  

AimWe evaluated the efficacy of a novel brain permeable “metformin-like” AMP-activated protein kinase activator, R481, in regulating glucose homeostasis.Materials and MethodsWe used glucose sensing hypothalamic GT1-7 neuronal cells and pancreatic αTC1.9 α-cells to examine the effect of R481 on AMPK pathway activation and cellular metabolism. Glucose tolerance tests and hyperinsulinemic-euglycemic and hypoglycemic clamps were used in Sprague-Dawley rats to assess insulin sensitivity and hypoglycemia counterregulation, respectively.ResultsIn vitro, we demonstrate that R481 increased AMPK phosphorylation in GT1-7 and αTC1.9 cells. In Sprague-Dawley rats, R481 increased peak glucose levels during a glucose tolerance test, without altering insulin levels or glucose clearance. The effect of R481 to raise peak glucose levels was attenuated by allosteric brain permeable AMPK inhibitor SBI-0206965. This effect was also completely abolished by blockade of the autonomic nervous system using hexamethonium. During hypoglycemic clamp studies, R481 treated animals had a significantly lower glucose infusion rate compared to vehicle treated controls. Peak plasma glucagon levels were significantly higher in R481 treated rats with no change to plasma adrenaline levels. In vitro, R481 did not alter glucagon release from αTC1.9 cells, but increased glycolysis. Non brain permeable AMPK activator R419 enhanced AMPK activity in vitro in neuronal cells but did not alter glucose excursion in vivo.ConclusionsThese data demonstrate that peripheral administration of the brain permeable “metformin-like” AMPK activator R481 increases blood glucose by activation of the autonomic nervous system and amplifies the glucagon response to hypoglycemia in rats. Taken together, our data suggest that R481 amplifies the counterregulatory response to hypoglycemia by a central rather than a direct effect on the pancreatic α-cell. These data provide proof-of-concept that central AMPK could be a target for future drug development for prevention of hypoglycemia in diabetes.


2015 ◽  
Vol 32 (1) ◽  
pp. 279
Author(s):  
Virginia Soldino ◽  
Ángel Romero-Martínez ◽  
Luis Moya-Albiol

Violence and/or delinquency in women have been masked to some extent by society. Thus, the main goal of this work is to deeply analyse the published works on these matters, in order to understand this phenomenon from a neurobiological perspective. Firstly, the theory of the cycle of violence as a facilitating mechanism of violence in women will be analysed, with a special emphasis on neuroanatomical correlates. Subsequently, the relation between drug consumption and violence in women will be explained. Finally, the main biological correlates known as facilitating mechanisms of violence in women will be exhaustively described. The main risk factors for the facilitation of violence and/or delinquency in women are mistreatment experiences during childhood and drug consumption. Furthermore, high levels of cortisol and testosterone and low levels of serotonin and oxytocin would be correlates of that violence. On the other hand, two types of aggressors have been described according to the response of the Autonomic Nervous System: the premeditated ones, who present a low reactivity, and the impulsive ones, who present a psychophysiological hyper-reactivity. As it is a complex and insufficiently studied issue, increasing the corpus of knowledge in this topic is necessary with the objective of developing effective programmes of treatment and/or prevention.


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