Browsing by Author "Beleslin, D.B. (7006410616)"

The emetic action of dopmaine, norepinephrine, epinephrine, nicotine, dimethylphenyl-piperazinium (DMPP), and 4-m-chlorophenylcarbamoyloxy-2-butynyltrimefhylammonium (McN-A-343) injected intracerebroventricularly (i.c.v.) to the unanesthetized cat was investigated and compared. ED50 values (mg) were as follows: nicotine, 0.011; epinephrine, 0.047; norepinephrine, 0.57; DMPP, 0.9; dopamine, 1.66; and McN-A-343, 4.42. The most potent was nicotine, whereas the least active McN-A-343. On the other hand, DMPP produced the longest emetic response, about 30 min, while McN-A-343-induced emesis lasted up to 1 min. The ablation of the area postrema abolished the emetic response to i.c.v. dopamine, norepinephrine, epinephrine, nicotine, and DMPP. However, the emetic response to i.c.v. McN-A-343 was significantly reduced in cats with an ablated area postrema. Taken together, the results obtained show that the area postrema is almost always involved in the central regulation of emesis and that the area postrema represents, in most cats, a common site of confluence of different inputs subserving the emesis. © 1989 Plenum Publishing Corporation.

The emetic action of dopmaine, norepinephrine, epinephrine, nicotine, dimethylphenyl-piperazinium (DMPP), and 4-m-chlorophenylcarbamoyloxy-2-butynyltrimefhylammonium (McN-A-343) injected intracerebroventricularly (i.c.v.) to the unanesthetized cat was investigated and compared. ED50 values (mg) were as follows: nicotine, 0.011; epinephrine, 0.047; norepinephrine, 0.57; DMPP, 0.9; dopamine, 1.66; and McN-A-343, 4.42. The most potent was nicotine, whereas the least active McN-A-343. On the other hand, DMPP produced the longest emetic response, about 30 min, while McN-A-343-induced emesis lasted up to 1 min. The ablation of the area postrema abolished the emetic response to i.c.v. dopamine, norepinephrine, epinephrine, nicotine, and DMPP. However, the emetic response to i.c.v. McN-A-343 was significantly reduced in cats with an ablated area postrema. Taken together, the results obtained show that the area postrema is almost always involved in the central regulation of emesis and that the area postrema represents, in most cats, a common site of confluence of different inputs subserving the emesis. © 1989 Plenum Publishing Corporation.

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Both noradrenaline and clonidine, injected into the cerebral ventricles, induced dose-dependent and shortlasting emesis in cats. Intracerebroventricular yohimbine, but not prazosin, inhibited the emesis evoked by noradrenaline. In contrast, both intracerebroventricular yohimbine and prazosin did not significantly change the clonidine-induced emesis. The ablation of the area postrema impaired the noradrenaline, but not the clonidine-induced emesis. It is postulated that the emesis produced by noradrenaline is mediated through alpha-2 adrenoceptors within the area postrema, whereas clonidine acted on emetic detectors outside chemoreceptor trigger zone in the area postrema most probably within the brainstem areas. These detectors are at least as sensitive to emetic stimuli as those within the area postrema. Moreover, chemical stimuli originating from the cerebrospinal fluid can induce emesis through these detectors without the area postrema.

Effects of the gaglionic stimulants, nicotine, dimethylphenylpiperazinium and tetramethylammonium on the isolated strips of longitudinal and circular muscles from the body of human and feline stomach were investigated. Tetramethylammonium produced concentration-dependent contractions of isolated preparations of either longitudinal or circular muscles of both species. Nicotine induced concentration-dependent relaxation only of the feline circular muscle strips. On the other hand, dimethylphenylpiperazinium had no significant effects on isolated strips of the longitudinal and circular muscles from the body of human and feline stomach. The differences in the effects of the ganglionic stimulants most probably reflect distinct anatomical sites of actions as well as nicotinic and muscarinic receptors in nervous structures and possibly smooth muscles of the human and feline gastric body. In addition, the ability of nicotine, but not of dimethylphenylpiperazinium and tetramethylammonium, to relax only the circular strips of the feline gastric body might indicate the existence of an unusual subtype of nicotinic receptors through which nicotine stimulates the inhibitory enteric ganglia.

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The effect of tropisetron and morphine injected intravenously upon emesis caused by oral copper sulphate was investigated in unanaesthetized cats. Morphine, but not tropisetron, inhibited the emetic response to copper sulphate. Only the inhibition of percentage of cats showing emesis was dose-dependent. The most sensitive to the inhibitory effect of morphine was number of vomits. These results suggest that morphine might be a putative central inhibitory neurotransmitter, although its peripheral effect cannot be excluded with certainty. In addition, the present experiments support the view that morphine is a broad spectrum antiemetic drug.

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Sympathetic nerve fibers in the gastrointestinal tract are derived from neurons in prevertebral ganglia, and terminate around intrinsic neurons of intestinal plexuses and in sphincter muscles. Sympathetic innervation of intestinal smooth muscles and mucosal cells is sparse. Noradrenaline is released from sympathetic nerve terminals, and acts via alpha and beta adrenergic receptors located on neuronal and effector cells throughout the gastrointestinal tract. Sympathicus exerts tonic activity on the intestinal blood flow and secretions, but not on motility. However, sympathetic stimulation results in the inhibition of propulsive activity of the gut. In extreme conditions, stress, pain, abdominal irritation, intestinal obstruction induce excessive activation of sympathetic inhibitory pathways in the gut, and may cause adynamic ileus, which can be relieved by alpha-2 receptor blocking drugs, and possibly by beta-blockers. Pharmacological effects of drugs acting on adrenergic mechanisms vary along the gastrointestinal tract and between species. Their therapeutical use is rather limited and in many instances controversial.

The intracerebroventricular administration of angiotensin II in pentobarbital-anesthetized cats produced dose-dependent increases in the arterial blood pressure without significant changes in the heart rate. The ablation of the area postrema significantly reduced, but did not abolish, the pressor effect of angiotensin injected into the cerebral ventricles. It follows, then, that the central pressor effect of angiotensin is dependent on the integrity of the area postrema and that this central site, at least in part, contributes to the pressor action of endogenous angiotensin. © 1989 Plenum Publishing Corporation.

The intracerebroventricular administration of angiotensin II in pentobarbital-anesthetized cats produced dose-dependent increases in the arterial blood pressure without significant changes in the heart rate. The ablation of the area postrema significantly reduced, but did not abolish, the pressor effect of angiotensin injected into the cerebral ventricles. It follows, then, that the central pressor effect of angiotensin is dependent on the integrity of the area postrema and that this central site, at least in part, contributes to the pressor action of endogenous angiotensin. © 1989 Plenum Publishing Corporation.

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