Modulation of the pressor response elicited by carbachol and electrical stimulation of the amygdala by muscarinic antagonists in conscious rats.

1. The nature of the muscarinic receptor involved in mediating cardiovascular changes caused by unilateral microinjection of carbachol (5 nmol) into, and electrical stimulation (200-300 microA) of, the amygdaloid complex was investigated in conscious, unrestrained female Sprague-Dawley rats. 2.

Pathways mediating CRF-induced inhibition of gastric emptying in rats.

The corticotrophin-releasing factor (CRF) is shown to be released during stress suggesting that CRF has a physiological role in the mediation of central nervous system (CNS) response to stress, including an inhibitory effect on gastric emptying. In the present study, we have examined the pathways by which intracerebroventricularly (i.c.

The role of brain acetylcholine in GABAA receptor antagonist-induced blood-pressure changes in rat.

Previous experimental studies have shown that intracerebroventricular (i.c.v.

A-4, a tertiary amine analog of HC-3, lowers arterial pressure in spontaneously hypertensive rats.

The 4-methyl piperidine analog (A-4) of hemicholinium-3 is a tertiary amine. A-4, like hemicholinium-3, inhibits sodium-dependent, high-affinity choline transport. The present study examined whether central cholinergic systems are involved in the expression of genetic hypertension.

A-ring ortho-disubstituted aporphine derivatives as potential agonists or antagonists at serotonergic 5-HT1A receptors.

(R)- And (S)-11-hydroxy-10-methylaporphine 1 and 2 are, respectively, a potent, highly specific serotonergic (5-HT1A) agonist and antagonist. In an ongoing structure-activity study, racemates of the positional isomers 8-hydroxy-9-methyl- and 8-methyl-9-hydroxyaporphine were prepared by modifications of literature methods and were resolved. The methyl ethers of the target compounds were also evaluated pharmacologically.

Prevention of organophosphate-induced toxicity in mice.

bis-Quaternary amines, which are acetal analogues of hemicholinium-3, were synthesized and several compounds were potent chemicals to antagonize toxicity induced by the organophosphate, paraoxon. Structural requirements were specific and included two oxygen atoms (bis-acetal substitution) within 6 or 7 atom heterocyclic rings, oxygen atoms spaced 2-carbon atoms from the quaternary nitrogen, and carbonyl substitutions adjacent to the spacing moieties, either bicyclohexyl or biphenyl. Biological testing showed a positive potency correlation between the chemicals when data from the following tests were compared: antagonism in mice of paraoxon-induced motor impairment using the incline screen and toxicity, and ability to induce contractions of guinea-pig isolated ilea.

Cardiovascular effects of centrally active cholinomimetics in conscious and anesthetized rats: the role of amygdala.

Central cardiovascular effects of cholinergic agonists depend on the dose, site and mode of administration, species, and to the state of the animal. Intravenous injection of physostigmine and intracerebroventricular injection of carbachol produced pressor and tachycardic responses in urethane-anesthetized rats. Both agents also elicited pressor responses in conscious rats, but bradycardia occurred in the presence of anesthesia.

Reversal of hemorrhagic shock in rats by oxotremorine: the role of muscarinic and nicotinic receptors, and AV3V region.

In an experimental model of hemorrhagic shock resulting in the death of almost all rats within 20-30 min, centrally active cholinomimetic drugs are reported to induce a prompt, sustained and dose-dependent improvement in blood pressure and survival rate claimed to be due to nicotinic, but not muscarinic actions. In the present study, cholinergic receptor agonist, oxotremorine (50 micrograms/kg, i.v.

Central muscarinic M2 cholinoceptors involved in cholinergic hypertension.

Cholinomimetic agents increase blood pressure and heart rate via central muscarinic cholinoceptors in various species. It was reported that i.c.

The effect of nordihydroguaiaretic acid on leukotriene C4 and prostaglandin E2 production following different reperfusion periods in rat brain after forebrain ischemia correlated with morphological changes.

Leukotriene C4 (LTC4) and prostaglandin E2 (PGE2) are the 5-lipoxygenase and cyclooxygenase metabolites of arachidonic acid (AA). They constrict blood vessels and enhance vascular permeability inducing vasogenic edema that may hurt the ischemic penumbra after cerebral ischemia and reperfusion. Nordihydroguaiaretic acid (NDGA) is known as the most potent inhibitor of 5-lipoxygenase in different tissues.

Are m-cholinoceptors of guinea pig gallbladder smooth muscle of m4 subtype?

The antagonism of carbachol-induced contractions of guinea pig gallbladder smooth muscle strips via selective antagonists, methoctramine, HHSiD, pf-HHSiD and DABDMA has been investigated in order to find out the m-cholinoceptor subtype(s) of gallbladder smooth muscle. All m-cholinoceptor antagonists examined, displaced the concentration-response curves to the right parallel in a concentration-dependent manner without affecting the maximum response. Schild analysis of data was consistent with competitive antagonism.

Effect of methylene blue on blood pressure in rats.

Methylene blue (MB) is a soluble guanylate cyclase inhibitor, and known as an endothelium-derived relaxing factor (EDRF) inhibitor in vitro. In the present study, it was demonstrated that intravenous administration of MB caused a dose-dependent hypertensive effect in rats. The hypertensive responses to the higher doses (10 and 20 mg/kg) of MB was followed by a reflex hypotension which did not appear in pithed rats.

Prostaglandin E2 and leukotriene C4 levels following different reperfusion periods in rat brain correlated with morphological changes.

Prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) are the metabolites of arachidonic acid (AA) that increase in forebrain following global ischemia and reperfusion. These mediators are highly potent vasoconstrictors of cerebral arteries leading to enhanced vascular permeability that induces the formation of vasogenic edema. In this study, after developing an experimental animal model simulating the concept of ischemic penumbra in the rat, the levels of PGE2 and LTC4 produced in the forebrain were measured and the effects of these mediators in short duration and prolonged reperfusion were investigated and then correlated with neuropathological findings.

Muscarinic receptor subtypes of guinea-pig common bile duct.

The antagonism of carbachol-induced contractions of guinea-pig common bile duct smooth muscle strips by various antagonists has been investigated in order to find out the muscarinic receptor subtype(s) of common bile duct smooth muscle. Atropine, pirenzepine, 4-DAMP and AF-DX 116 were used as nonselective, M1-selective, M1- and M3-selective and M2-selective muscarinic antagonists, respectively. All muscarinic antagonists examined displaced the concentration-response curves to the right, parallelly and in a concentration-dependent manner, without affecting maximum response.