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Functional contribution of autonomic innervation to urethral striated sphincter: studies with parasympathomimetic, parasympatholytic and alpha-adrenergic blocking agents in spinal cord injury and control male subjects.

Mechanisms underlying urethral pressure changes at the external sphincter region after administration of neuropharmacologic agents were investigated with cystosphincterometric studies and electromyography of the external urethral sphincter in adult patients with spinal cord injury and control male subjects. Bethanechol chloride, propantheline or phentolamine were administered to 37 spinal cord injury men and 3 normal controls. After cystectomy 3 additional spinal cord injury patients were subjected to bethanechol studies. The results of these studies suggested that the pressure changes in the external sphincter zone were caused predominantly by the concurrent changes produced in the detrusor and/or the smooth muscle components of the proximal urethra and of the external sphincter zone.

Adolescent↗

Biosynthesis of slaframine, (1S,6S,8aS)-1-acetoxy-6-aminooctahydroindolizine, a parasympathomimetic alkaloid of fungal origin. 3. Origin of the pyrrolidine ring.

The phytopathogen Rhizoctonia leguminicola has previously been shown to incorporate pipecolic acid into the piperidine alkaloids 1-acetoxy-6-aminooctahydroindolizine (slaframine) and 3,4,5-trihydroxyoctahydro-1-pyrindine. In the experiments described here, resting cultures of R. leguminicola were incubated with [1-14C]- and [2-14C]malonic acid and with [1-14C]- and [2-2H]acetic acid. Both acids were incorporated into the ring systems of both alkaloids. Mass spectrometric analysis of 2H-enriched slaframine showed that the label resides in the five-membered ring and that the methyl carbon of acetate is joined to the carboxyl carbon of pipecolate. A pipecolate-dependent decarboxylation of [1-14C]malonate was demonstrated in cell-free extracts of R. leguminicola. The results account for previously unattributed carbons in the two alkaloids and suggest the formation of an eight-carbon intermediate common to both alkaloids by acylation of malonate with pipecolic acid.

Acetates↗

Biosynthesis of slaframine, (1S,6S,8aS)-1-acetoxy-6-aminooctahydroindolizine, a parasympathomimetic alkaloid of fungal origin. 4. Metabolic fate of ethyl pipecolylacetate, 1,3-dioxooctahydroindolizine, and 1-hydroxyoctahydroindolizine in Rhizoctonia leguminicola.

Known or suspected intermediates in the biosynthesis of slaframine and 3,4,5-trihydroxyoctahydro-1-pyrindine, piperidine alkaloids of the phytopathogenic fungus Rhizoctonia leguminicola, were prepared and tested for biological conversions. Ethyl pipecolylacetate, an analogue of the postulated condensation product of pipecolic and malonic acids (two previously identified alkaloid precursors), was insufficiently stable for feeding experiments. The lactam of pipecolylacetate, 1,3-dioxooctahydroindolizine, was degraded by the fungus without direct incorporation into alkaloids. The known slaframine precursor 1-hydroxyoctahydroindolizine was prepared by a novel route which permitted high levels of deuterium enrichment at C-1 and C-3. Mass spectrometric examination of the slaframine biosynthesized from cis- and trans-[1,3,3-2H]-1-hydroxyoctahydroindolizine strengthened arguments that 1-oxooctahydroindolizine is an intermediate in slaframine biogenesis.

Carbon Radioisotopes↗

Parasympathomimetic influence of carbachol on local cerebral blood flow in the rabbit by a direct vasodilator action and an inhibition of the sympathetic-mediated vasoconstriction.

1 Two sorts of effect of carbachol on local cerebral blood flow (caudate nucleus) have been studied: (a) a direct action on the arterial smooth muscle; (b) an interaction with the adrenergic (sympathetic) constrictor system which innervates the vascular system of this nucleus. 2 Continuous measurements of the following variables were performed in lightly anaesthetized rabbits: local blood flow (caudate nucleus), arterial blood pressure, PaO2, PaCO2. 3 After blockade of the nicotinic synapses in the superior cervical sympathetic ganglion by local hexamethonium injection, carbachol was infused into the common carotid artery, thus minimizing systemic effects of this drug. Infusions of 0.6, 1.3 and 2.5 micrograms kg-1 min-1 induced mean increases in caudate blood flow of about 8, 17 and 37% respectively, without notable modifications of other variables measured. 4 The dilator effect of 2.5 micrograms kg-1 min-1 carbachol was reduced to a mean of 12% after intravenous injection of 0.5 mg/kg atropine, and could be totally abolished by higher doses (1 to 1.5 mg/kg). 5 Administration of 2.5 micrograms kg-1 min-1 of carbachol diminished by more than 50% the reduction in caudate blood flow induced by postganglionic stimulation of the cervical sympathetic chain, but did not affect the reduction of flow obtained by intravenous infusion of noradrenaline (2.5 to 5.0 micrograms kg-1 min-1). This inhibition of the adrenergic (sympathetic) system by carbachol was not modified by high doses of atropine (1 mg/kg i.v.). 6 We conclude that: (a) the local cerebral blood flow of a deep structure can be significantly modified by activation of vascular muscarinic receptors; (b) activation of non-muscarinic prejunctional cholinoceptors can cause inhibition of the sympathetic fibres innervating the vascular bed of the same structure.

Animals↗

[Acetylcholine in the bovine retina and the parasympathomimetic effect of pilocarpine].

Using titrations of acetylcholine (ACh) on guinea-pig ileum the authors have demonstrated that there is no significant statistical difference between the cholinergic activity of extracts of 150 mg of retinal tissue from pilocarpinised eyes (0.3 mug of ACh) and the activity of extracts from control eyes not subjected to pilocarpine (0.29 mug of ACh). The pilocarpine had been instilled into the bovine conjunctival sac at the rate of three drops of 3 p. 100 pilocarpine HCl ten times at intervals of three minutes. One hour after the last application the animals were killed and the eyes enucleated. The role of pilocarpine in the regulation of tissues in the posterior segment of the eye is discussed.

Acetylcholine↗