Depressor effects of muscarinic and non-muscarinic mediation induced by lateral hypothalamic stimulation in the rat

Summary Transient sympathetically-mediated depressor effects were induced by stimulation of a small locus in the lateral hypothalamic peri-fornical region, medial to the fields of Forel. The ganglionic blocking agent, atropine methyl nitrate (ATMN), was used to show that muscarinic as well as non-muscarinic sympathetic ganglion receptor neurotransmission was involved. Evidence is presented that stimulation of this LH site co-activates a number of mechanisms and that depending on which of these are activated, the ganglionic blocking agent ATMN may either block, reverse or potentiate the depressor effect.     

Histamine receptors in the cat mesenteric circulation.

The distribution of histamine receptors was studied in the isolated perfused vascular bed of the cat terminal ileum. The results indicated that the depressor effect of histamine is mediated through the stimulation of metiamide-sensitive H2-receptors, while the pressor effect of the amine is mediated by the stimulation of mepyramine-sensitive H1-receptors.     

The effect of L-dopa on pupillary diameter in mice

Summary Injection of L-dopa in mice produces dose-dependent mydriasis. Pre-treatment with peripheral dopa-decarboxylase inhibitors (carbidopa and benserazide) or with an alpha-adrenergic blocking agent (phentolamine) abolishes the pupillary dilation caused by L-dopa. Pretreatment with fusaric acid, an inhibitor of dopamine-beta-hydroxylase, also antagonizes the mydriatic effect of L-dopa. Thus, our results suggest that the mydriasis produced in mice following the injection of L-dopa is caused by its peripheral conversion to noradrenaline, which stimulates alpha-adrenergic receptors in the dilator iridis. There was no evidence that stimulation of specific dopaminergic receptors was involved.We are grateful to N. Rothschild, Head of Laboratory Animal Department, Sackler School of Medicine, for his help.     

Histamine receptors in the cat mesenteric circulation

Summary The distribution of histamine receptors was studied in the isolated perfused vascular bed of the cat terminal ileum. The results indicated that the depressor effect of histamine is mediated through the stimulation of metiamidesensitive H₂-receptors, while the pressor effect of the amine is mediated by the stimulation of mepyramine-sensitive H₁-receptors.The authors are indebted to Dr.W. A. M. Duncan, Research Institute, Smith Kline and French Laboratories, Welwyn Garden City, Hertfordshire, England, for his generous gift of metiamide. This work is supported in part by Eczacibasi Research Found. Levent, Istanbul, Turkey.     

Action of N-butylnorsympathone on the effects of cardioaccelerator nerve stimulation in the dog]

In Dogs anaesthetized with pentobarbital (30 mg . kg-1), N-butylnorsympathone (20 mg . kg-1 i.v.) reduced the bradycardia induced by stimulating the cardiac nerve (1, 2, 5, 10 Hz). Phentolamine (1 mg . kg-1 i.v.) or yohimbine (0.3 mg . kg-1 i.v.), two potent alpha-adrenoceptor blocking agents known to block presynaptic alpha-adrenoceptor induced a recovery of the effect of cardiac nerve stimulation. Prazosine (0.050 mg . kg-1 i.v.) an alpha-adrenoceptor blocking agent known to be ineffective on presynaptic alpha-adrenoceptors did not induce a recovery. However neither phentolamine or yohimbine were able to prevent the effects of N-butylnorsympathone. Neither haloperidol (0.050 to 2 mg . kg-1 i.v.) or pimozide (0.20 to 1 mg . kg-1 i.v.) induced a recovery or prevented the effects of N-butylnorsympathone. These results suggest that N-butylnorsympathone may stimulate presynaptic receptors which do not resemble classical presynaptic alpha-adrenoceptors or dopamine receptors.     

The effects of dopaminergic blocking agents on the glucose tolerance test in 6 humans and 6 dogs.

Pre-treatment with low doses of sulpiride, an atypical dopaminergic blocking agent, but not haloperidol, a classical dopaminergic blocking agent, decreased tolerance to glucose and increased blood serotonin levels in 6 normal humans and 6 normal dogs investigated.     

The principal toxin of Delphinium brownii Rydb., and its mode of action.

Examination of D. brownii, a stock-poison of Western Canada, revealed that the principal toxin was methyllycaconitine: a potent neuromuscular blocking agent which appears to act competitively at nicotinic receptors.     

Enhanced depressor reflex by stimulation of superior cervical ganglion and by propranolol

Summary The systemic depressor reflex in cats evoked by inflation of an intrasinusal balloon is enhanced by stimulation of the superior cervical ganglion and by close infusion of 20g/ml/min of (d, 1) propranolol.This work was supported by grant No. 22600-1 NIH, Heart, Lung and Blood Institute, Bethesda, MD.     

Pharmacologic study of several alpha-adrenolytics

Six alpha-adrenoceptor blocking agents have been investigated in dogs and rats. 170 150 and 170 153 have been found the most potent of these agents. At low doses (0,1 microgram/kg) they reversed the pressor response to low doses of adrenaline (0,1 and 0,3 microgram/kg) and suppressed the response to high doses of adrenaline. They reduced the pressor response to noradrenaline. In addition, in dogs 170 150 increased the tachycardia caused by stimulation of the cardiac nerve. The compound prevented and reversed the inhibition caused by clonidine on the effects of cardiac nerve stimulation. 170 153 did not increase the tachycardia caused by cardiac nerve stimulation, but it prevented and reversed the inhibitory effects of clonidine on this stimulation. The results show that 170 150 and 170 153 are potent alpha-adrenoceptor blocking agents acting on both pre and post-synaptic alpha-adrenoceptors which could be interesting pharmacological tools.     

Hymenin, a novel alpha-adrenoreceptor blocking agent from the Okinawan marine sponge Hymeniacidon sp

A novel bromine-containing alkaloid, hymenin, has been isolated from the Okinawan marine sponge Hymeniacidon sp. as a potent alpha-adrenoceptor blocking agent and its structure determined to be 1 on the basis of the spectral data.     

The principal toxin ofDelphinium brownii Rydb., and its mode of action

Summary Examination ofD. brownii, a stock-poison of Western Canada, revealed that the principal toxin was methyllycaconitine: a potent neuromuscular blocking agent which appears to act competitively at nicotinic receptors.We thank the University of Calgary, The National Research Council of Canada, and the Alberta Agriculture Department, for financial assistance.     

Zur Blutdruckwirkung von Aludrin und Adrenalin

Summary The depressor action of small doses of adrenaline on the blood pressure (B.P.) of the decapitated cat may be abolished by pretreatment with pilocarpine; atropine restores the original depressor action. The fall in B.P. due to adrenaline after ergotamine once more becomes an increase when pilocarpine has been given earlier. After atropine a fall in B.P. again occurs. This effect of pilocarpine and atropine on a depressor response has already been described in the case of Aludrine (N-isopropyl-noradrenaline) byFromherz.     

The effect of L-Dopa on the spinal monosynaptic mass reflex

Summary After i. v. injection of reserpine, the monosynaptic mass reflex (MSMR) is depressed in spinalized cats. However, the complete recovery of MSMR was obtained 30 min after L-Dopa application. Pimozide, a dopamine-receptor blocking agent, blocked this action of L-Dopa. It is presumed that dopaminergic receptors are involved in the action of L-Dopa on spinal MSMR.     

Serotonergic and cholinergic interaction in the regulation of pituitary-adrenal function in rats

It has been proposed that the central serotonergic inputs which modulate pituitary-adrenal secretion are mediated by cholinergic neurons. We have tested this hypothesis in intact rats. Male Sprague-Dawley rats were injected with cholinergic and serotonergic agents which enhanced transmitter function and with receptor blocking agents. Agents were injected, singly and in combination, into both unstressed and stressed animals. Since the response to cholinergic agents might be due to changes to vasopressin release, Brattleboro (vasopressin deficient) rats were also injected with cholinergic agents. The level of plasma corticosterone at 1-h post-injection was determined. Results indicate that the serotonin receptor blockade decreased the stimulatory, cholinergic effect of physostigmine. Cholinergic receptor blockers did not significantly reduce the corticosterone rise induced by 5-hydroxytryptophan. These results do not support the hypothesis of cholinergic mediation of serotonergic input. Nicotinic and muscarinic receptors appeared to exert opposing influences on the system. The nicotinic receptor antagonist was able to block the stimulatory effect of physostigmine. The muscarinic receptor antagonist significantly elevated plasma corticosterone levels. No differences were found in the effect of physostigmine on Brattleboro rats as compared to controls. These data are interpreted as suggesting that 1) the acetylcholine-induced stimulation of pituitary-adrenal function is mediated, in part, by serotonergic neurons; and 2) stimulation of nicotinic receptors is facilitatory whereas stimulation of muscarinic receptors is inhibitory to pituitary-adrenal function.     

Effect of angiotensin II on neonatal lamb carotid arteries.

Isometric tension was measured in arterial strips from neonatal lambs and adult sheep, after stimulation by angiotensin II. During the early maturation period immediately following birth (3 weeks) there was a progressive increase in sensitivity to the agent.     

Hymenin,a novel α-adrenoceptor blocking agent from the Okinawan marine spongeHymeniacidon sp.

Summary A novel bromine-containing alkaloid, hymenin, has been isolated from the Okinawan marine spongeHymeniacidon sp. as a potent -adrenoceptor blocking agent and its structure determined to be1 on the basis of the spectral data.     

Effet inhibiteur de la tétrabénazine sur l'influence corticosurrénalienne de la réserpine

Summary Reserpine provokes an intense and long-lasting (more than 20 h) stimulation of the adrenocortical activity of the rat. Tetrabenazin (50 mg/kg) also produces an adrenocortical stimulation which is, however, of a much shorter duration. The injection of tetrabenazin 1 h before the injection of reserpine (5 mg/kg) prevents the prolonged stimulating effect of reserpine on the adrenal cortex. This effect can be compared with the blocking effect of tetrabenazin, a short-acting central depressant with monoamine-liberator properties, against the prolonged central sedative influence of reserpine.     

Frequency-dependent effect of verapamil on rat soleus muscle

In the presence of verapamil (0.1 mM) rat soleus muscle fibers failed to generate action potentials with overshoots. In fibers with their Vm set to a local level of -90 mV, verapamil produces a gradual reduction in the amplitude of the repetitive action potentials; this effect is more pronounced at high rates of stimulation (100 Hz). Our results suggest a local anesthetic action of this drug that could contribute with its calcium channel blocking effect to the diminished mechanical tension observed in the presence of the drug.     

Metabolic energy requirements during teleost melanophore adaptations

Inhibition of oxidative phosphorylation by 2,4-dinitrophenol or sodium cyanide promotes complete melanosome aggregation in teleost melanophores. This aggregation is not promoted via the alpha-sympathetic receptor sites because it occurs in the presence of tolazoline hydrochloride, an alpha-receptor blocking agent. Interpretation of these results suggests metabolic energy release is required in the centrifugal direction only.     

Modification of the effect of cardio-accelerator nerve stimulation in dogs by clonidine and several alpha-adrenolytics]

In dogs anaesthetized with pentobarbital (30 mg. kg -1 i.v.), clonidine (0,01 mg.kg-1 i.v.) reduced the tachycardia induced at low frequencies by stimulation of the cardiac nerve. The effects of some alpha-adrenoceptor blocking agents on this effect have been studied. Small doses of yohimbine (0.3 mg. kg-1 i.v.) or piperoxan (0.3 mg. kg-1 i.v.) increased the effects of the stimulation and in addition antagonized the inhibitory effects of clonidine and reversed the pressor response to adrenaline. Thymoxamine (1 mg.kg-1 i.v.) and prazosin (1 mg.kg-1 i.v.) did not increase the effect of the stimulation of the cardiac nerve, but reduced the effect of clonidine. ARC239 (0.05 mg.kg-1) reversed the pressor response to adrenaline but even at high doses did not increase the effects of the stimulation of the cardiac nerve or the effects of clonidine. These observations afford further evidence for a dissimilarity between pre and post-synaptic alpha-adrenoceptors.