Acetylcholine synthesis and its dependence on nervous activity.

The findings discussed in this paper mainly derived from studies on salivary glands, serving as model organs, indicate that the capacity to form the neurotransmitter acetylcholine, as judged by the activity of choline acetyltransferase, is influenced by the traffic of nerve impulses, as a long term effect. In the glands, choline acetyltransferase seems to be exclusively localized to the cholinergic nerves. In the postganglionic parasympathetic nerves of the glands, the activity of choline acetyltransferase decreases when the flow of secretory impulses in these nerves is abolished or reduced either by isolating the nerves from the central nervous system, surgically or pharmacologically, or by diminishing the reflex activation of the glands from the mouth. The opposite occurs when the reflex activation of the salivary glands is enhanced, i.e. the activity of choline acetyltransferase increases. Observations on various other organs are quoted in support of the view that the traffic of nerve impulses is of importance for the activity of the enzyme. An increase in choline acetyltransferase activity also occurs in some salivary glands after sympathetic denervation. This puzzling observation is discussed in relation to impulse traffic. Increased nerve impulse traffic and collateral sprouting seem to be responsible for the rapid restitution of choline acetyltransferase activity from a low level in an organ partially deprived of its cholinergic nerve supply.     

Effect of botulinum toxin on the choline acetyltransferase activity in salivary glands of cats

Summary The choline acetyltransferase activity of submandibular glands that had previously received a retrograde injection of botulinum toxin via their ducts was found to be markedly lower than in the untreated contralateral glands. In the parotid glands exposed to the same treatment the activity of this enzyme was less affected.This work was supported by grants from the Wellcome Foundation to S. K. K. and J. R. G., and from the Faculty of Medicine in Lund to J. E.     

Corticosteroid effects on cholinergic enzymes in ethanol-treated fetal brain cell cultures

Summary In the presence of ethanol, corticosterone and dexamethasone inhibit choline acetyltransferase and acetylcholinesterase activities in cultured fetal brain cells of the rat. These results suggest that corticosteroids may have an important influence on the activity of cholinergic enzymes in the fetal brain and may antagonize the effects of ethanol in this setting.     

Corticosteroid effects on cholinergic enzymes in ethanol-treated fetal brain cell cultures

In the presence of ethanol, corticosterone and dexamethasone inhibit choline acetyltransferase and acetyl-cholinesterase activities in cultured fetal brain cells of the rat. These results suggest that corticosteroids may have an important influence on the activity of cholinergic enzymes in the fetal brain may antagonize the effects of ethanol in this setting.     

The possibility of centrifugal projections to the retina in the rat

In rats, glutamic acid decarboxylase activity increased in the proximal portion of the optic nerve after its ligation, whereas the activities of choline acetyltransferase and tyrosine hydroxylase remained constant. Possible centrifugal neurons to the retina are GABAergic.     

The possibility of centrifugal to the retina in the rat

Summary In rats, glutamic acid decarboxylase activity increased in the proximal portion of the optic nerve after its ligation, whereas the activities of choline acetyltransferase and tyrosine hydroxylase remained constant. Possible centrifugal neurons to the retina are GABAergic.     

Discharge pattern analysis suggests existence of a low-threshold calcium channel in cold receptors.

The regular periodic activity patterns of mammalian cold receptors have been quantitatively studied. Analysis of the timing of either single impulses or impulse groups demonstrated that the periodic receptor process is maintained independently of impulse generation and continues to operate under conditions when afferent impulses are not initiated. These results imply that the underlying conductances must be operational at threshold potentials related to impulse generation. In addition to temperature, the periodic process is considerably sensitive to calcium, which affects mainly the probability of impulse generation during each cycle. Reduction of external calcium and application of calcium entry blockers with relative selectivity for low-threshold calcium channels are similarly effective in modulating cold receptor activity. The data imply the existence of a low-threshold calcium conductance at the sensory terminal.     

Discharge pattern analysis suggests existence of a low-threshold calcium channel in cold receptors

Summary The regular periodic activity patterns of mammalian cold receptors have been quantitatively studied. Analysis of the timing of either single impulses or impulse groups demonstrated that the periodic receptor process is maintained independently of impulse generation and continues to operate under conditions when afferent impulses are not initiated. These results imply that the underlying conductances must be operational at threshold potentials related to impulse generation. In addition to temperature, the periodic process is considerably sensitive to calcium, which affects mainly the probability of impulse generation during each cycle. Reduction of external calcium and application of calcium entry blockers with relative selectivity for low-threshold calcium channels are similarly effective in modulating cold receptor activity. The data imply the existence of a low-threshold calcium conductance at the sensory terminal.     

Altered brain cholinergic enzymes activity in the genetically obese rat

Genetically obese male Zucker rats (fa/fa) and their lean littermates (Fa/-) were used in this experiment. Fourteen-week-old obese and lean littermates were sacrificed and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) enzymes were assayed in specific brain regions. The assays of these enzymes indicate that obese animals had a significantly lower ChAT activity in the cerebellum, pons, and cerebral cortex and a significant increase in ChAT activity in the thalamus and hypothalamus. Meanwhile, the cerebral cortex, cerebellum, midbrain, thalamus and hypothalamus of the obese animals showed significantly higher AChE activity than their lean littermates. It was concluded from this study that obesity may be associated with changes in the enzymes of the brain cholinergic system.     

Nervous control of smooth muscle by transmitters,cotransmitters and modulators

Conclusion The part played by peripheral neuroeffector control mechanisms has been underestimated. These are additional to central and ganglionic control mechanisms and are much more elaborate than originally thought. While the classical view is that the autonomic nervous system consists largely of antagonistic cholinergic and adrenergic nerves, about sixteen putative neurotransmitters have been proposed in autonomic nerves in the past few years, including various monoamines, polypeptides, purines and amino acids. Modulatory transmitter mechanisms have also been recognized, including prejunctional inhibition or enhancement of transmitter release, postjunctional modulation of transmitter action, and the secondary involvement of locally synthesized hormones and prostaglandins. The existence of more than one transmitter substance in some nerves is now widely recognized, and suggestions have been made about the ways that this can lead to differential peripheral control mechanisms at nerve terminals themselves. The cotransmitters always have synergistic actions on postjunctional effector cells, but two different operating mechanisms are postulated. 1) If both substances are stored in the same vesicles (for example, ACh or NA with ATP), release is closely parallel at all impulse frequencies. Upon release, the cotransmitter, in addition to having a direct action on postjunctional cells, may facilitate the action of the other transmitter and/or act as an inhibitor of its release. Differential actions at different impulse frequencies are achieved post-junctionally by ATP and NA acting via EJP-spike and spike-independent mechanisms, respectively. 2) If the two substances are stored in separate vesicle types (for example ACh or NA with some peptides), then differential release is possible at different impulse frequencies; the peptides released at higher frequencies modulate the role of the classical transmitter, by both prejunctional enhancement of its release and post-junctional facilitation of its action.     

Intracellular recording of secretory potentials in a "mixed" salivary gland.

Secretory potentials evoked by nerve stimulation have been recorded from both types of cell (peripheral and central) present in the acini of cockroach salivary glands.     

The relationship of phosphodiesterase and cyclic AMP to the process of fluid secretion in the salivary glands of the ixodid tick Amblyomma americanum.

Phosphodiesterase (PDE) activity in the salivary glands of the female. Amblyomma americanum decreased as the tick progressed from a slow to a rapid phase of feeding, while the rate of fluid secretion increased when glands were stimulated with cyclic AMP and theophylline. Dopamine stimulated PDE activity and an 'inhibitory' factor was found in glands obtained from rapidly engorging ticks which decreased PDE activity. These findings are discussed as they relate to the process of fluid secretion by salivary glands of feeding ixodid ticks.     

Altered brain cholinergic enzymes activity in the genetically obese rat

Summary Genetically obese male Zucker rats (fa/fa) and their lean littermates (Fa/-) were used in this experiment. Fourteen-week-old obese and lean littermates were sacrificed and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) enzymes were assayed in specific brain regions. The assays of these enzymes indicate that obese animals and a significantly lower ChAT activity in the cerebellum, pons, and cerebral cortex and a significant increase in ChAT activity in the thalamus and hypothalamus. Meanwhile, the cerebral cortex, cerebellum, midbrain, thalamus and hypothalamus of the obese animals showed significantly higher AChE activity than their lean littermates. It was concluded from this study that obesity may be associated with changes in the enzymes of the brain cholinergic system.This work was supported by a grant from the National Aeronautics and Space Administration (NAG 2-411), a grant from the National Institutes of Health (NIH RR 0811), and a grant from the Division of Research Resources, National Institutes of Health (NIH Grant RR 03020).     

Ricerche fisiologiche sulla distribuzione periferica del nervo depressore aortico destro nel cane

Summary The periferal distribution of the right aortic nerve has been studied in physiological experiments on the dog. It has been found that after section of both Hering's nerves and left vago-depressor trunk and after denervation of the baroceptor area ofMuratori-Nonidez lying at the root of the right subclavian artery, the electrical stimulation of one splancnic nerve or the intravenous injection of adrenaline still produces a reflex bradycardia; moreover the cooling of the vagus nerve still results in a rise of the blood pressure. It is inferred that a group of baroceptor fibres of the right aortic nerve originate from areas situated in the aortic region.     

Regulatory peptides in the respiratory system

Many regulatory peptides have been described in the respiratory tract of animals and humans. Some peptides (bombesin, calcitonin, calcitonin gene-related peptide) are localised to neuroendocrine cells and may have a trophic or transmitter role. Others are localised to motor nerves. Vasoactive intestinal peptide and peptide histidine isoleucine are candidates for neurotransmitters of non-adrenergic inhibitory fibres and may be cotransmitters in cholinergic nerves. These peptides may regulate airway smooth muscle tone, bronchial blood flow and airway secretions. Sensory neuropeptides (substance P, neurokinin A and B, calcitonin gene-related peptide) may contract airway smooth muscle, stimulate mucus secretion and regulate bronchial blood flow and microvascular permeability. If released by an axon reflex mechanism these peptides may be involved in the pathogenesis of asthma. Other peptides, such as galanin and neuropeptide Y, are also present but their function is not yet known.     

Regulatory peptides in the respiratory system

Summary Many regulatory peptides have been described in the respiratory tract of animals and humans. Some peptides (bombesin, calcitonin, calcitonin gene-related peptide) are localised to neuroendocrine cells and may have a trophic or transmitter role. Others are localised to motor nerves. Vasoactive intestinal peptide and peptide histidine isoleucine are candidates for neurotransmitters of non-adrenergic inhibitory fibres and may be cotransmitters in cholinergic nerves. These peptides may regulate airway smooth muscle tone, bronchial blood flow and airway secretions. Sensory neuropeptides (substance P, neurokinin A and B, calcitonin gene-related peptide) may contract airway smooth muscle, stimulate mucus secretion and regulate bronchial blood flow and microvascular permeability. If released by an axon reflex mechanism these peptides may be involved in the pathogenesis of asthma. Other peptides, such as galanin and neuropeptide Y, are also present but their function is not yet known.     

Demilune cells of the cat submandibular gland; an unlikely source of kallikrein

The functional significance of kallikrein in the salivary gland remains unclear partially because of uncertainty over its precise cellular localization. Kallikrein was thought to originate in acinar cells, until recent evidence from cat and rat localized it primarily to the ducts. The possibility that salivary kallikrein may also be located in demilune cells was investigated in this study. - The total kallikrein content of cat submandibular glands was found to be substantially reduced by sampathetic nerve stimulation; whereas parasympathetic stimulation had no significant effect. These biochemical findings did not correlate with morphological studies that revealed almost complete depletion of the demilune cells secretory granules after stimulation of either division of the autonomic nerve supply. This lack of correlation makes it unlikely that kallikrein is present in the demilune cell secretory granules.     

Interaction of vasoactive intestinal peptide (VIP) with cholinergic stimulation of glucagon secretion

Summary VIP-containing nerve fibers as well as cholinergic nerve fibers have a ubiquitous distribution in the body and both types of nerves have been demonstrated to innervate the pancreatic islets. The present study shows, in the intact, conscious mouse, that VIP and the cholinergic agonist carbachol stimulate glucagon secretion in a dose-dependent manner. Furthermore VIP and carbachol were found to exert potentiating interactions on glucagon secretion. These results suggest the existence of an interactive neural regulation of glucagon secretion, exerted by acetylcholine and VIP.We thank Professor V. Mutt, Karolinska Institutet, Stockholm, for giving us VIP. The skilful technical assistance of Lena K vist and Peter Okmark is gratefully acknowledged. This study was supported by grants from the Swedish Medical Research Council (14P-4289, 14X-4286) and the Medical Faculty, University of Lund, Sweden.     

Organophosphate-mediated inhibition of choline acetyltransferase activity in rat brain tissue

Administration of the organophosphate compound soman in rats resulted in an inhibition of choline acetyltransferase activity in almost all brain regions examined. Enzyme activity was inhibited by 20-50% in various brain regions 30 min after soman injection (94-120 micrograms/kg). Enzyme activity in two regions decreased with time to a near zero level by 3 h after injection.     

The relationship of phosphodiesterase and cyclic AMP to the process of fluid secretion in the salivary glands of the ixodid tickAmblyomma americanum

Summary Phosphodiesterase (PDE) activity in the salivary glands of the female.Amblyomma americanum decreased as the tick progressed from a slow to a rapid phase of feeding, while the rate of fluid secretion increased, when glands were stimulated with cyclic AMP and theophylline Dopamine stimulated PDE activity and an inhibitory factor was found in glands obtained from rapidly engorging ticks which decreased PDE activity. These findings are discussed as they relate to the process of fluid secretion by salivary glands of feeding ixodid ticks.Journal article No. 3360 of Agricultural Experiment Station, Oklahoma State University, Stillwater, Oklahoma. This research was supported in part of NSF grant PCM-24140A02 from the National Science Foundation.