Effects of midbrain stimulation and iontophoretic application of serotonin, noradrenaline, morphine and GABA on electrical thresholds of afferent C- and A-fibre terminals in cat spinal cord

We have used the single-fibre excitability testing method to investigate whether electrical stimulation in midbrain periaqueductal gray or lateral reticular formation, as well as intraspinal iontophoretic application of the suspected inhibitory neurotransmitters serotonin (5-hydroxytryptamine), noradrenaline, the opiate morphine, or gamma-aminobutyric acid (GABA), exert presynaptic actions at the central terminals of cutaneous afferent unmyelinated or myelinated fibres. Thresholds to antidromically excited 42 single unmyelinated and 18 myelinated fibres in the sural nerve by intraspinal microstimulation were determined before and during periaqueductal gray or lateral reticular formation stimulation (3 100 ms trains/s at 100 Hz; 100-900 microA) or intraspinal iontophoretic application (40-300 nA) of 5-hydroxytryptamine, noradrenaline, morphine or GABA from a multibarrel micropipette. Periaqueductal gray or lateral reticular formation stimulation had mixed effects on unmyelinated and myelinated fibre thresholds, with most threshold measurements within +/- 10% of control. There was a tendency for thresholds to increase more during periaqueductal gray than lateral reticular formation stimulation. Thresholds of unmyelinated fibres were predominantly raised during iontophoretic application of 5-hydroxytryptamine (20/29 fibres), noradrenaline (10/13) and morphine (15/21), while GABA had mixed effects; thresholds of nearly all myelinated fibres were raised by each drug. Both periaqueductal gray or lateral reticular formation stimulation and application of 5-hydroxytryptamine, noradrenaline or morphine tended to raise thresholds in the majority of the 53 unmyelinated and myelinated fibres tested. Methodological problems in interpreting the physiological significance of these results for presynaptic modulation are discussed.     

The Evolution of Vascular Smooth Muscle Responses to Histamine and 5-Hydroxytryptamine

Studies on the vascular smooth muscle responses to histamine and 5-hydroxytryptamine and on the distribution of these amines in different tissues were performed in several species of reptiles. The responses to adrenaline, noradrenaline and acetylcholine were studied for comparison. Vascular actions were recorded both in vivo as changes in systemic arterial blood pressure and in vitro as changes in vascular resistance in perfused preparations. The specificity of the action of each drug was evaluated by means of pharmacological blocking agents. Tissue levels of histamine and 5-hydroxytryptamine were determined spectrofluorometrically. Fluorescence microscopy was used for histochemical localization of the histamine stores. The results indicate that histamine and 5-hydroxytryptamine exert dual actions (inhibitory and stimulatory) on reptilian vascular smooth muscles which have thus acquired response patterns towards these amines similar to those found in mammals. Inhibitory as well as stimulatory actions of adrena line, noradrenaline and acetylcholine are also present in reptiles. Levels of 5-hydroxytrypt amine are apparently low in most tissues, whereas many species show very high tissue levels of histamine. Histamine, except that of the stomach, is mainly located in tissue mast cells and blood basophils. Nutritional-dependent variations in mast cell number are parallelled by varia tions in tissue histamine content. By comparing the present results with those previously ob tained in jawless vertebrates, fish and amphibians, a general outline of the evolution of vascular actions and tissue stores of histamine and 5-hydroxytryptamine is presented.     

Effects of chlorpromazine on hypothalamic aminergic neurons and stress responses in moderate cold

Summary Guinea-pigs were treated with chlorpromazine or 0.9% NaCl and exposed to +4° C or +23° C for 2 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5HT), 3-methoxy-4-hydroxyphenylethylene-glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum and urinary catecholamines, muscle and liver glycogen and blood glucose were also measured. Chlorpromazine caused deep hypothermia at this moderately cold temperature and slight hypothermia at room temperature. Cold increased the activity of noradrenergic and serotonergic neurons, as indicated by the increase in hypothalamic MHPG and 5-HIAA and also the MHPG∶NA and 5-HIAA∶5-HT ratios. A tendency towards drug-induced inhibition of hypothalamic serotonergic neurons was seen, although this was not significant. A drug-induced inhibition of noradrenergic neurons could not be ruled out. Increased drug-induced turnover of DA was observed in the cold, and a tendency in the same direction was seen at room temperature. Excretion of DA into the urine was induced by chlorpromazine. The hypothermic guinea-pigs had low serum catecholamines, indicating diminished sympathetic activity, but high urinary catechols, a sign of cold stress.     

Comparison of effects of monoamines on transmission in spinal pathways from group I and II muscle afferents in the cat

Summary The actions of noradrenaline (NA) and 5-hydroxytryptamine (5-HT; serotonin) were compared with those of L-3,4-dihydroxyphenylalanine methyl ester (Methyl-L-DOPA) on transmission to spinal interneurones in mid-lumbar (L4 and L5) segments of the cat spinal cord. The drugs were applied ionophoretically and their effects were tested on monosynaptic field potentials evoked by nerve impulses in hindlimb group I and group II muscle afferent fibres and on responses of interneurones with synaptic input from these fibres. Of field potentials recorded at various locations, both NA and 5-HT depressed those evoked from group II fibres in the intermediate and ventral horn regions of the spinal cord but not, or only occasionally, in the dorsal horn. Field potentials of group I origin were not depressed. The tested interneurones were located where group II field potentials were affected. NA, 5-HT and Methyl-L-DOPA depressed responses to electrical stimulation of group II fibres but not responses evoked by group I fibres. The depression consisted of an increase in the latency and a decrease in the number of action potentials evoked by the stimuli. All three drugs were also found to decrease the amplitude of intracellularly recorded monosynaptic EPSPs of group II origin but not of monosynaptic EPSPs evoked in the same neurones by group I fibres. Interneuronal firing induced by DL-homocysteic acid was depressed as effectively as responses to electrical stimulation of peripheral nerves. The possibility of presynaptic and/or postsynaptic mechanisms of the selective depression of synaptic actions of group II origin are discussed.     

Functional difference in monoamine transmitters in the behaviorally abnormal mouse mutant (wriggle mouse sagami)

A mutant mouse (wriggle mouse sagami, WMS) with neurological disorders was found in a colony of the BALB/c strain. The clinical signs included tremor, dystonia and involuntary movements. The concentrations of the neurotransmitter substances, noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) and acetylcholine (ACh), were measured simultaneously with their metabolites in dissected brain regions by high-performance liquid chromatography with electrochemical detection. The turnover of 5-HT was significantly higher in the cerebral cortex, hippocampus, hypothalamus, midbrain and pons-medulla of WMS than of the genetic control, BALB/c. The intrastriatal DA and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid were increased. However, there was no evidence to suggest an increase in turnover rate of this neurotransmitter. An increase in concentration of and decrease in turnover rate of NA were observed in the cerebellum of this mutant. These findings suggest that multiple disturbance of the neurotransmitter system was largely responsible for the manifestation of the clinical signs of WMS.     

45Ca efflux from anterior byssus retractor muscle in phasic and catch contraction.

Phasic or catch contractions in Mytilus anterior byssus retractor muscle (ABRM) were activated by acetylcholine (ACh) and catch relaxation was initiated by 5-hydroxytryptamine (5HT). During phasic contraction and early in catch there is a brief increase in 45Ca efflux. When catch occurs, there is a subsequent drop in 45Ca efflux which then slowly recovers as catch tension declines. With catch relaxation by 5HT there is a biphasic increase in 45Ca efflux, identical to that seen when 5HT is applied to resting muscle. Compartment analyses based on the magnitude of pairs of these responses at varying times of the washout indicated that the increase in 45Ca efflux with activation originates from a compartment with the same time constant as the intermediate (80--100 min) compartment already described by previous resting efflux experiments. The decrease in 45Ca efflux during catch also involves this compartment. The increase in 45Ca efflux with 5HT originates from a more slowly exchanging Ca store with a time constant of approximately200 min.     

The responses of cortical neurones to monoamines under differing anaesthetic conditions

1. Noradrenaline, isoprenaline, 5-hydroxytryptamine and acetylcholine have been applied into the environment of single neurones in the cat cerebral cortex by micro-iontophoresis. The influence of anaesthesia on the neuronal responses to these drugs was studied.2. In general, excitation of neurones by noradrenaline occurred commonly in both unanaesthetized encéphale isolé (48%) and N(2)O-halothane anaesthetized preparations (57%) while depressions were less frequent (24 and 20% respectively). The picture differed markedly in barbiturate anaesthetized animals where excitation was uncommon (12%) and the majority of cells (59%) was depressed by noradrenaline. Although fewer cells were studied, similar differences were obtained with isoprenaline and 5-hydroxytryptamine for the three types of preparation. In sharp contrast, the vast majority of cells was excited by acetylcholine in each of the preparations: encéphale isolé 84%; N(2)O-halothane 92%; barbiturate anaesthetized preparations 85%.3. The differing neuronal responses observed in these experimental situations were not the result of variations in the depth of anaesthesia.4. Although the depths at which neurones were encountered within the cortex did not differ in N(2)O-halothane and encéphale isolé preparations, significantly more cells were found in deeper layers of cortex in barbiturate preparations. The proportion of cells excited or depressed by noradrenaline was generally similar at each depth in the three preparations used.5. The distribution of rates of cell firing was strikingly similar in each preparation, and most of the cells studied had frequencies below 10/sec.6. The direction in which a cell responds to noradrenaline is mainly determined by the type of anaesthetic used, and not by the depth of anaesthesia, the rate of cell firing, or cell depth within the cortex. This suggests important differences in the central pharmacology of halothane and barbiturates.     

Effects of oxiracetam on neurotransmitter release from rat hippocampus slices and synaptosomes.

The effects of the nootropic drug oxiracetam on the K(+)-evoked overflow of [3H]D-aspartic acid ([3H]D-ASP), [3H]acetylcholine ([3H]ACh), [3H] gamma-aminobutyric acid ([3H]GABA), [3H]noradrenaline ([3H]NA) and [3H]5-hydroxytryptamine ([3H]5-HT) have been studied in superfused rat hippocampal slices. The overflow of [3H]D-ASP was enhanced by low concentrations of oxiracetam (0.01-1 microM) but not by high concentrations (10-100 microM) which showed some tendency to inhibit it. Similarly, low concentrations of oxiracetam increased, although less effectively, the depolarization-evoked overflow of [3H]ACh, whereas higher concentrations were without effect. At the concentrations active on [3H]D-ASP and [3H]ACh overflow oxiracetam did not affect that of [3H]GABA, [3H]NA or [3H]5-HT. The oxiracetam effects present in slices could not be observed in hippocampal synaptosomes. Thus oxiracetam may selectively increase the release of glutamate and acetylcholine in hippocampus by a mechanism which appears not to be sited in the releasing nerve terminals.     

Noradrenaline and 5-hydroxytryptamine release in the hippocampus during seizures induced by hippocampal kindling stimulation: an in vivo microdialysis study

The intracerebral microdialysis technique has been used to monitor extracellular levels of noradrenaline, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the rat hippocampus in vivo in response to focal and generalized seizures induced by hippocampal kindling stimulation. In fully kindled animals a stimulus-induced generalized seizure gave rise to a three-fold increase of noradrenaline levels in the stimulated hippocampus as compared to baseline levels (15-min samples). The maximal increase of noradrenaline levels occurred within the first minutes after onset of seizure activity, as assessed in 2-min sample fractions with the noradrenaline uptake blocker desipramine added to the perfusion medium. After the peak increase, the noradrenaline levels tapered off, reaching baseline after 8-10 min. In 6-hydroxydopamine-treated animals, baseline noradrenaline levels were markedly reduced and there was no significant increase in noradrenaline release in response to a generalized seizure. These data support the hypothesis that the high extracellular levels of noradrenaline measured in seizures are of neuronal origin. There were no significant changes in extracellular 5-hydroxytryptamine or 5-hydroxyindoleacetic acid levels after a generalized seizure. In non-kindled animals the steady state noradrenaline levels during uptake blockade were two-three times higher than in the kindled rats. However, the peak noradrenaline levels measured in both hippocampi after the first two electrical kindling stimulations giving rise to focal epileptiform activity (afterdischarge) were similar to those observed in the kindled animals in response to generalized seizures. The increase of noradrenaline release in the non-kindled animals was significantly correlated to the duration of afterdischarge. In conclusion, the present study demonstrates the usefulness of the intracerebral dialysis technique for monitoring noradrenaline, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid release during seizures. The results indicate that both focal and generalized hippocampal seizures evoked by electrical kindling stimulation lead to a marked increase of transmitter release from noradrenergic but not from serotonergic neurons in the hippocampus. The ability of the noradrenergic system to respond by increased transmitter release to epileptic seizures is thus retained also in the kindled state.     

Changes in smooth muscle sensitivity to agonist drugs during development.

The receptors in the expansor secundariorum muscle of chicks were characterized pharmacologically and the changes in their response to nerve stimulation and agonist drugs determined during development. The muscle responded to noradrenergic nerve stimulation, noradrenaline and 5-hydroxytryptamine without any change in sensitivity during development. Expansor muscles from 15-day-old chicks were more sensitive to isoprenaline than muscles from older animals. The muscle from 15-day-old chicks responded to acetylcholine and histamine; the sensitivity to both drugs decreased progressively with increasing age of the chicks and disappeared by day 40 posthatching. The normal developmental decrease in response to acetylcholine and histamine were prevented by surgical denervation of the muscle; an intervention that also induced supersensitivity to noradrenaline greater than isoprenaline greater than 5-hydroxytryptamine. The muscle responded to potassium chloride without any change in sensitivity during development or following surgical denervation. These findings indicate that sympathetic nerves influence the responsiveness of the expansor secundariorum muscle to drugs, especially the development decrease in response to acetylcholine and histamine.     

Acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine affects the adrenal glands as well as the brain in the marmoset

A parkinsonian syndrome was induced in marmosets by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 4 days. Ten days following the onset of drug administration, brainstem and adrenal tissues were assayed for levels of monoamines and their metabolites. In the brainstem tegmentum, dopamine, its metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC), and noradrenaline were reduced, whereas 5-hydroxytryptamine (5-HT) levels were elevated, in comparison with untreated controls. In the adrenal gland, 5-HT and adrenaline levels were unchanged, but dopamine and noradrenaline were substantially elevated.     

Slow postsynaptic potentials in neurones of submucous plexus of guinea-pig caecum and their mimicry by noradrenaline and various peptides

Intracellular recordings of membrane potential and membrane currents were made from neurones in the submucous plexus of the guinea-pig caecum in vitro. Fast and slow excitatory postsynaptic potentials and slow inhibitory postsynaptic potentials were recorded from the majority of neurones following focal stimulation of presynaptic fibres in the plexus. The slow inhibitory postsynaptic potential was associated with an increase in membrane conductance and reversed its polarity at -90 mV; it was reversibly blocked by yohimbine. The slow excitatory postsynaptic potential and its underlying current was associated with a decrease in membrane conductance. Two kinds of voltage-dependence both of the slow excitatory postsynaptic potential and current were observed; in 80% of cells, the excitatory postsynaptic potential and current became smaller with membrane hyperpolarization and reversed polarity at -90 mV (reversing type) but in 20% of cells both the excitatory postsynaptic potential and current simply disappeared when the membrane potential reached -70 mV (non-reversing type). The effects of acetylcholine, adenosine 5'-triphosphate, bombesin, 5-hydroxytryptamine, neurotensin, noradrenaline, substance P and vasoactive intestinal polypeptide were examined. The only substance which mimicked the slow inhibitory postsynaptic potential was noradrenaline; brief applications of noradrenaline caused hyperpolarizations which had the same time-course, reversal potential and sensitivity to yohimbine as the slow inhibitory postsynaptic potential. The non-reversing type of slow excitatory postsynaptic potential was mimicked only by adenosine 5'-triphosphate. The reversing type of slow excitatory postsynaptic potential was mimicked by bombesin, neurotensin, substance P and vasoactive intestinal polypeptide. 5-Hydroxytryptamine and vasoactive intestinal polypeptide (in some neurones) caused a depolarization with an increase in membrane conductance. All three synaptic potentials were reversibly depressed by superfusion of noradrenaline but noradrenaline did not affect the potential changes evoked by brief application of exogenous acetylcholine or substance P. It is concluded that, in guinea-pig submucous plexus neurones, the slow inhibitory postsynaptic potential is mediated by noradrenaline and results from a potassium conductance increase.(ABSTRACT TRUNCATED AT 400 WORDS)     

Production of corticotrophin releasing hormone by the isolated hypothalamus of the rat.

1. The ability of the rat hypothalamus to produce corticotrophin releasing hormone (CRH) in vitro was studied in the presence and absence of neurotransmitter substances, angiotensin and corticosterone. 2. Acetylcholine, 5-hydroxytryptamine (5-HT) and angiotensin II increased hypothalamic CRH release and content. 3. Noradrenaline and glycine decreased the spontaneous release of CRH from the hypothalamus but neither of these substances affected hypothalamic CRH content. 4. Dopamine, GABA, adrenaline, melatonin, histamine, glutamic acid and corticosterone did not affect the basal CRH activity of the hypothalamus in vitro. 5. Noradrenaline, GABA and corticosterone reduced the acetylcholine- and 5-HT-induced increases in the release of CRH from the hypothalamus. The rises in CRH content induced by acetylcholine and 5-HT were also reduced by noradrenaline and GABA but increased by corticosterone. 6. The physiological significance of the results and the potential value of the technique are discussed.     

Role of central alpha 2-adrenoceptors on the development of muricidal behavior in olfactory bulbectomized rats: effect of alpha 2-adrenoceptor antagonists

Upon surgical removal of olfactory bulbs, by the 8th to 10th day after the surgery muricidal behavior has been demonstrated in 75.4% of rats. In the homogenates of forebrain obtained from rats demonstrating muricidal behavior, levels of noradrenaline, 5-hydroxytryptamine and their metabolites (i.e., 3-methoxy-4-hydroxyphenylglycol sulfate and 5-hydroxyindoleacetic acid) were not changed. However, the fractional turnover rate of noradrenaline in the forebrain of the olfactory bulbectomized rats was significantly decreased without alterations in the metabolism of 5-hydroxytryptamine when compared to that of the sham rats. The muricidal behavior and the aggressiveness were suppressed by antagonists of alpha 2-adrenoceptors (yohimbine, idazoxan and rauwolscine), but not by the alpha 1-adrenoceptor antagonist (corynanthine). Furthermore, upon administration of yohimbine or idazoxan to rats demonstrating the muricidal behavior, the level of noradrenaline in the homogenates of forebrain was decreased while that of 3-methoxy-4-hydroxyphenylglycol sulfate was increased. The maximum binding capacity (Bmax) of [3H]yohimbine to the forebrain membranes obtained from the olfactory bulbectomized rats was significantly higher than that from the sham rats without demonstrating any differences in dissociation constants (Kd) between the two brain membranes. Based on these results, it was suggested that olfactory bulbectomy has caused some functional changes in central alpha 2-adrenoceptors.     

In vivo evidence that 5-hydroxytryptamine (5-HT) neuronal firing and release are not necessarily correlated with 5-HT metabolism.

The relationship between 5-hydroxytryptamine release, metabolism and unit activity has been investigated in the anaesthetized rat. 5-Hydroxytryptamine release and metabolism were monitored in vivo by the measurement of extracellular 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the frontal cortex using in vivo voltammetry combined with nafion-coated and uncoated electrically pretreated carbon fibre electrodes. The monoamine oxidase inhibitor pargyline (100 mg/kg) increased extracellular 5-hydroxytryptamine and decreased 5-hydroxyindoleacetic acid. The 5-hydroxytryptamine releaser fenfluramine (10 mg/kg i.p.) acutely increased extracellular 5-hydroxytryptamine while having no effect on 5-hydroxyindoleacetic acid and the effect on extracellular 5-hydroxytryptamine was markedly reduced in rats pretreated (four weeks) with 5,7-dihydroxytryptamine. 8-Hydroxy-2-(di-n-propyl-amino) tetralin (10 micrograms/kg i.v.), an agonist at the 5-hydroxytryptamine1A somatodendritic autoreceptor, inhibited 5-hydroxytryptamine neuronal firing in the dorsal raphe nucleus and decreased extracellular 5-hydroxytryptamine during the period when firing was inhibited but did not alter extracellular 5-hydroxyindoleacetic acid. In contrast 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridin-4-yl) (RU 24969), which is an agonist at the terminal autoreceptor in the rat, had no effect on 5-hydroxytryptamine neuronal firing but decreased 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. The results support the view that extracellular 5-hydroxyindoleacetic acid is not a good index of 5-hydroxytryptamine release and that under specific circumstances 5-hydroxytryptamine neuronal firing, release and metabolism are independent of one another.     

Effects of Alpha- and Beta-Receptor Blocking Agents on Catecholamine and 5-Hydroxytryptamine Induced Peroxidase and Amylase Secretion from Guinea Pig Submandibular Gland

Enzyme secretion from incubated guinea pig submandibular gland slices was induced by adrenaline, noradrenaline, dopamine, 5-hydroxytryptamine or dibutyryl cyclic AMP combined with theophylline. Effects of alpha- and beta-blocking agents on stimulated peroxidase and amylase discharge were studied. Propranolol (beta-blocker), but not phenoxybenzamine (alpha-blocker), markedly inhibited the secretion of both enzymes induced by adrenaline or noradrenaline. Dopamine and 5-hydroxytryptamine were found to be potent enzyme secretagogues. Both propranolol and phenoxybenzamine antagonized the effects of these two amines. The secretagogic effect of dibutyryl cyclic AMP in combination with theophylline was not affected by either propranolol or phenoxybenzamine. L-DOPA and 5-hydroxytryptophan were without effect on enzyme secretion. It is concluded that peroxidase and amylase are secreted in parallel from guinea pig submandibular gland and that enzyme release is mainly mediated via the beta-adrenergic receptor.     

A comparison of platelet aggregation produced by seven compounds and a comparison of their inhibitors

The aggregating effects of adenosine diphosphate, thrombin, 5-hydroxytryptamine, tryptamine, adrenaline and noradrenaline, and tri-ethyl tin have been carefully compared. The first three compounds in some circumstances produce remarkably similar effects although there are important differences. The kinetics of aggregation induced by adrenaline (and noradrenaline) are quite different and the tri-ethyl tin effects are different again. Anti-serotonins specifically inhibit 5-hydroxytryptamine and the anti-adrenaline drug phentolamine specifically inhibits the effects of the catecholamines.     

Hypothalamic receptors influencing the secretion of corticotrophin releasing hormone in the rat

1. The production of corticotrophin releasing hormone (CRH) by the rat hypothalamus in vitro was studied in the presence and absence of various neurotransmitter substances and drugs which mimic or antagonize their actions.2. Acetylcholine, nicotine and bethanechol increased, in a dose-related manner, hypothalamic CRH release and content but the maximal responses to bethanechol or nicotine were less than those to acetylcholine.3. The actions of acetylcholine were antagonized by atropine, pempidine and hexamethonium but were completely inhibited only when atropine and pempidine were given together. The effects of nicotine were abolished by pempidine but not by atropine while those of bethanechol were abolished by atropine but not by pempidine.4. Acetylcholine-induced hypothalamic CRH activity was also antagonized by cyproheptadine but not by methysergide.5. 5-Hydroxytryptamine caused dose-related increases in hypothalamic CRH release and content. Its effects were antagonized by cyproheptadine and methysergide but not by atropine, pempidine or hexamethonium.6. Acetylcholine-induced increases in hypothalamic CRH production were reduced by GABA, noradrenaline, adrenaline, methoxamine and phenylephrine but not by isoprenaline. The actions of GABA were antagonized by bicuculline and those of noradrenaline by phentolamine but not by atenolol.7. The results suggest the presence of nicotinic and muscarinic cholinoceptors, 5-hydroxytryptamine receptors, alpha-adrenoceptors and GABA-receptors within the hypothalamus all of which may be important in the control of CRH secretion.     

Effects of 3‘, 5’-Cyclic Adenosine Monophosphate, 5-Hydroxy-tryptamine,Noradrenaline and Theophylline on the Simultaneous Release of Peroxidase and Amylase from the Guinea Pig Submanibular Gland

Noradrenaline (NA), 5-hydroxytryptamine (5-HT) and N⁶,2-0′-dibutyryl cyclic adenosine monophosphate (DBcAMP) induced a parallel discharge of peroxidase and amylase from the guinea pig submandibular gland in vitro. Theophylline alone, at a concentration of 5 mM, had only little effect on enzyme secretion, but it markedly potentiated the effects of noradrenaline, 5-HT and DBcAMP at submaximal concentrations. Adenosine-3′-monophosphoric acid (3′-AMP) and adenosine-5′-monophosphoric acid (5′-AMP) were without effect on enzyme secretion. Maximal effects of NA and DBcAMP on enzyme release were obtained at concentrations of 0.01 mM and 3 mM respectively. Dose-response curves for the stimulation of peroxidase and amylase release by 5-HT revealed that this amine was a potent secretagogue at the concentrations of 0.1 and 0.3 mM but was less effective at higher concentrations. It is concluded that peroxidase and amylase are simultaneously secreted from the guinea pig submandibular gland, and that the release of both enzymes is mediated via cyclic AMP.     

The role of the endothelium in the control of venous tone: studies on isolated human veins

The role of the endothelium in the vasomotor control of veins was investigated in 14 isolated ring preparations of presumably normal saphenous veins obtained from vein grafts in connection with vascular surgery. The investigations were performed with the specimens mounted for recording isometric tension in organ baths. Paired rings were used, one normal and the other de-endothelialized by gentle rubbing. The responses to noradrenaline (10(-8)-2 X 10(-5) M), acetylcholine (10(-6) M) and 120 mM KCl solution were tested. After precontraction with 10(-7) M noradrenaline, acetylcholine at 10(-6) M did not induce cholinergic relaxation, but in the majority of experiments induced a further increase in tone. Maximal contraction with noradrenaline was significantly higher in normal compared to de-endothelialized vessels. Therefore, endothelium-derived relaxation as in arteries did not occur in human saphenous veins and the existence of an endothelial-derived contracting factor in response to acetylcholine and noradrenaline is a possibility.