Extracts of Cordyceps militaris lower blood glucose via the stimulation of cholinergic activation and insulin secretion in normal rats.

Previous studies have shown that Cordyceps militaris (CM) has a hypoglycemic effect, but the actual mechanism remains unclear. This study explored the hypoglycemic mechanism of aqueous extracts of CM in normal Wistar rats. First, the optimal dose of CM for lowering plasma glucose and insulin secretion was tested. Further, atropine and hemicholinium-3 (HC-3) were injected and a western blot was used to investigate insulin signaling. It was found that 10 mg/kg CM extracts had a stronger hypoglycemic effect than a higher dose (100 mg/kg); therefore, a dose of 10 mg/kg was used in subsequent experiments. In normal rats, CM extracts decreased plasma glucose by 21.0% and induced additional insulin secretion by 54.5% after 30 min. When atropine or HC-3 was injected, CM induced a hypoglycemic effect, but the enhancement of insulin secretion was blocked. By western blotting, significant increases in the insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT-4) were observed after CM feeding. However, the elevation of these signaling proteins was abolished by atropine or HC-3. Taken together, these findings indicate that CM can lower plasma glucose via the stimulation of insulin secretion and cholinergic activation involved in the hypoglycemic mechanism of normal Wistar rats.

Interaction of chlorphenvinphos with cholinergic receptors in the rabbit hypothalamus.

The purpose of this study was to find out whether chlorphenvinphos (CVP), an organophosphorous pesticide, interacts with the muscarinic cholinergic receptors in CNS. To attain this goal, the effects of intrahypothalamic injections of oxotremorine (Ox), a muscarinic agonist, and physostigmine (Phys), a carbamate anticholinesterase, were compared with those produced by intrahypothalamic injections of CVP in the rabbit. It was found that the infusion of Ox (20 micrograms) as well as Phys (200 micrograms) into the anterior hypothalamus leads to an increase in the 4-7 Hz theta rhythm in the hippocampus and to the appearance of behavioral symptoms suggestive of a threat response. In the case of Ox, the effects could be prevented by injections of 20 micrograms scopolamine, a muscarinic antagonist. Pretreatment of the hypothalamus with 100 micrograms hemicholinium (HC-3) did not prevent the effects of Phys injected 2 h later. (HC-3 prevents the resynthesis of acetylcholine by blocking choline reuptake. This leads to a gradual depletion of ACh stores and to an inhibition of the cholinergic transmission). It suggests that Phys activates directly postsynaptic muscarinic receptors. Intrahypothalamic injections of CVP in doses of up to 1360 micrograms produced no overt changes in behavior nor in the hippocampal EEG of the rabbit and did not prevent the effect of subsequent injections of Ox. This suggests that CVP is neither an agonist nor antagonist of the muscarinic receptors in the rabbit hypothalamus.

Effect of hemicholinium-3 on the hypothalamic concentration of a cytochemically detectable glucose-6-phosphate dehydrogenase-stimulating substance.

Hypothalamus and plasma of salt-loaded rats, spontaneously hypertensive rats (SHR), and hypertensive reduced renal mass rats (RRM), and the plasma of patients with essential hypertension and of Milan hypertensive rats contain an increased concentration of a cytochemically detectable glucose-6-phosphate dehydrogenase (G6PD)-stimulating substance that has properties similar to that of a possible choline derivative di-methyl methylene immonium ion. Intracerebroventricular (i.c.v.) administration of hemicholinium-3 (HC-3) selectively blocks high-affinity neuronal choline uptake, inhibits brain acetylcholine (ACh) synthesis, and decreases arterial pressure in SHR through an inhibiting effect on hypothalamic cholinergic function. The experiments were performed to study the effect of centrally administered HC-3 on the content of the cytochemically detectable cholinelike substance in hypothalamus and plasma of SHR. HC-3 or saline was infused into the lateral cerebral ventricle for 6 days with a minipump in 14 SHR. On day 7, the hypothalamic and plasma concentration of the cytochemically detectable substance was significantly reduced in rats that received HC-3. The hypothalamic concentration was 225 +/- 95.6 x 10(8) G6PD U per hypothalamus (range 38.2-775) in SHR that received saline and 1.037 +/- 0.45 x 10(8) G6PD U (range 0.112-3.61) (p < 0.05) in SHR that received HC-3. The respective plasma concentrations were 284.9 +/- 26 U/ml (range 192-374) and 72.7 +/- 14.7 U/ml (range 24-119) (p < 0.05). The findings are consistent with the physicochemical evidence, which suggests that the cytochemically detectable substance is a choline derivative.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine in the posterior hypothalamic nucleus is involved in the elevated blood pressure in the spontaneously hypertensive rat.

Intravenous injection of physostigmine, 40 and 80 ug/kg, in unanesthetized normotensive rats increased systolic blood pressure (SBP) by 21 +/- 3 and 42 +/- 7 mmHg. This pressor response was 80% inhibited by intracerebroventricular (icv) injection of hemicholinium-3 (HC-3), 20 ug. Simultaneous icv injection of HC-3 and choline (365 ug) prevented the inhibition of the pressor response by HC-3. In spontaneously hypertensive rats, injection of HC-3 either icv (20 ug) or bilaterally into the posterior hypothalamic nuclei (1 ug) decreased SBP by about 40 mmHg. The effect of intrahypothalamic HC-3 was completely blocked by simultaneous injection of choline (24.3 ug) into the same site. The hypotensive effect of icv HC-3 was completely blocked by icv choline (243 ug) and was inhibited up to 60% by injections of choline (24.3 ug) into the posterior hypothalamic nuclei.

The effects of intrahypothalamic hemicholinium-3 on muricide, irritability and feeding.

Male Long-Evans rats that consistently killed mice when food deprived were injected unilaterally in the lateral hypothalamus with 20 micrograms and 30 micrograms of the acetylcholine synthesis inhibitor hemicholinium-3 (HC-3) and saline in a counterbalanced order. Rats were evaluated 1, 2, 3, 24, 48 and 72 hours post-injection for effects on muricide, irritability and feeding. HC-3 suppressed muricide and feeding and produced a trend toward reduced irritability during the first three hours post-injection. These data indicate that modulation of cholinergic systems in the lateral hypothalamus influences several behaviors and not any one behavior specifically.