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Results for “Norepinephrine”

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PubMed1981

Increased hypothalamic norepinephrine metabolism after water deprivation in the rat.

Rat brain catecholamine metabolism was changed over a period of several days by limited access to water (10 min/day). One or two weeks limited access to water caused an increase in hypothalamic norepinephrine metabolism as measured with alpha-methyl-para-tyrosine. Brain stem and telencephalon norepinephrine was not affected by the limited access to water regimen. Dopamine metabolism in the corpus striatum and the hypothalamus was not altered by limited access to water. If the limited access to water was continued for 3 or more weeks, hypothalamic norepinephrine metabolism then returned to normal. The increase in hypothalamic norepinephrine metabolism was confirmed by a second method measuring in vivo tyrosine hydroxylase activity. Additional experiments demonstrate that this affect is specific for water deficits. Limited access to food had no effect on the metabolism of norepinephrine in the hypothalamus. Water deficits produced by replacing water with a 2% NaCl solution caused a similar increase in hypothalamic norepinephrine metabolism to that observed after one week limited access to water. Furthermore, 10 min access to water stopped the increased hypothalamic metabolism of norepinephrine seen after one week of limited access to water. The regional specificity (effect seen in hypothalamus but not the telencephalon and brain stem), and the stimulus specificity (water and not food deficits) suggest hypothalamic norepinephrine involvement in thirst or hormonal control of water regulation.

Animals↗

PubMed1986

Peripheral sympathectomy and adrenal medullectomy do not alter cerebrospinal fluid norepinephrine.

Despite a blood-brain barrier for norepinephrine, the concentration of norepinephrine in plasma and cerebrospinal fluid has been observed to be similar. This relationship between plasma and cerebrospinal fluid norepinephrine levels suggest that peripheral sympathetic neurons innervating blood vessels to brain and spinal cord may contribute significantly to cerebrospinal fluid norepinephrine levels, and questions the validity of cerebrospinal fluid norepinephrine as an index of central nervous system noradrenergic activity. We demonstrate that extensive destruction of the peripheral sympathetic nervous system and the adrenal medulla has no effect on rat cerebrospinal fluid norepinephrine. It is therefore unlikely that peripheral sources of norepinephrine contribute significantly to cerebrospinal fluid norepinephrine levels.

Adrenal Glands↗

PubMed1978

alpha- and beta-receptor blockade of isoproterenol- and norepinephrine-induced effects on regional blood flow and blood flow acceleration.

The effects of the beta-receptor blocking agent propranolol (100 microgram/kg i.v.) and of the alpha-receptor blocking agent dihydroergotamine (50 microgram/kg i.v.) on hemodynamic responses to isoproterenol and norepinephrine (both 1--1024 ng/kg) were investigated in anesthetized dogs. The effects studied were: (1) flow in the ascending aorta and the coronary, common hepatic, gastroduodenal, splenic, cranial mesenteric, renal and femoral arteries: (2) maximal flow acceleration in the splenic, cranial mesenteric and femoral arteries; (3) maximal rate of change of left ventricular pressure (LV dP/dt max). Propranolol shifted the dose-response curves for the isoproterenol-induced flow increases in the common hepatic, gastro-duodenal, and cranial mesenteric arteries to the right. It did not influence the flow responses to isoproterenol in the ascending aorta or the coronary, splenic, renal and femoral arteries. Propranolol prevented the decrease of arterial pressure evoked by isoproterenol. Propranolol shifted the isoproterenol-induced increase of LV dP/dt max and maximal blood flow to the same extent. Propranolol blocked the flow to the liver and gastrointestinal tract to a greater extent than the LV dP/dt max and maximal flow acceleration. Propranolol had no effect on the norepinephrine-induced increases in flow in the splenic, femoral and coronary arteries, but blocked the norepinephrine-evoked increases of flow accelerations and LV dP/dt max to the same extent. Dihydroergotamine inhibited the norepinephrine-induced increase in flow in the femoral artery and the decreases in flow in the hepatic, splenic, cranial mesenteric and renal arteries, and reversed the reduction of flow in the gastroduodenal artery. It is argued that dihydroergotamine may inhibit the increase in femoral flow through two mechanisms: (1) blocking the flow reduction to norepinephrine in the abdomen, and thereby passively shunting blood from the abdomen in preference to the femoral bed; (2) attenuating the norepinephrine-evoked reflexogenic femoral vasodilatation. It is concluded that: (1) propranolol is a beta-receptor blocking agent with a preference for blockade of isoproterenol-induced vascular effects; (2) norepinephrine-induced flow increases are not direct actions on vascular beta-receptors; (3) the increase of maximal blood flow accelerations after isoproterenol and norepinephrine is mediated by stimulation of cardiac beta-receptors; (4) dihydroergotamine is an alpha-receptor blocking agent particularly in the splanchnic vascular region.

Adrenergic alpha-Antagonists↗

PubMed1991

Relationship between myocardial tissue norepinephrine and coronary flow heterogeneity.

The purpose of this study was to investigate the hypothesis that heterogeneity of myocardial tissue norepinephrine content exists and is one of the controllers of flow heterogeneity in the canine myocardium. Tissue norepinephrine content was measured simultaneously with coronary blood flow in multiple sections of the left ventricle of eight anesthetized open-chest dogs. Radioactive microspheres were used for the measurement of blood flow during baseline and sympathetic stimulation. The left ventricle was cut into 15 subepicardial and 15 subendocardial sections. Norepinephrine levels of these same tissue sections were measured using high-pressure liquid chromatography. The average control coronary blood flow was 92.4 +/- 19.5 ml/min/100 g. Ansa subclavia stimulation (10-msec duration, 18-24 V, 10 impulses/sec) increased coronary blood flow to 127.9 +/- 21.9 ml/min/100 g. The average of the norepinephrine levels was 2480 +/- 573 ng/g wet wt and the biological variation was almost four times the method variation. The within-animal coefficient of variation was 32.9%. No significant regional differences were found in flow or norepinephrine content. Regression analysis between the percentage of mean norepinephrine (PNE) and the percentage of mean control flow (Pflow) produced the equation: Pflow = 0.29 (PNE) + 70.4 (r = 0.44, P less than .0001). The equation for PNE vs percentage of stimulated flow is Pflow = 0.24 (PNE) + 76.2 (r = 0.48, P less than .0001). Thus, significant heterogeneity of tissue norepinephrine levels exists in the heart. There also appears to be a direct linear relationship between tissue norepinephrine content and coronary blood flow distribution in the canine myocardium.

Animals↗

PubMed1977

Central and peripheral norepinephrine metabolism in rat strains selectively bred for differences in response to stress.

Rats of the Maudsley nonreactive (MNRA) strain were found to contain higher levels of norepinephrine in heart, spleen, and hypothalamus than animals of the Maudsley reactive (MR) strain. Total adrenal catecholamines were also greater in nonreactive animals. There was a trend toward higher endogenous norepinephrine concentration in MR rats in brainstem and telencephalon, but this was not statistically significant. Turnover measurements calculated from the fall of norepinephrine at 1 and 4 hours after a single dose of levo-alpha-methylparatyrosine showed no significant strain differences in telencephalon or brainstem, but MNRA animals had a faster rate of norepinephrine decline in heart than had MR rats. Possibly indicative of a higher rate of norepinephrine metabolism, the percentage of 3H-non-catechol metabolites relative to total counts was higher in brainstem of MNRA rats 90 min after intraventricular injection of 3H-norepinephrine. However, the disagreement between this estimate of norepinephrine metabolism and that provided by the alpha-methyl-paratyrosine technique prevents a conclusive statement about norepinephrine metabolism in the two strains. The results are discussed in the light of the established differences in behavior between the strains as well as other work exploring relationships between catecholamine metabolism and emotionality.

Adrenal Glands↗

PubMed1992

Effects of S-11701 on accumulation, release and metabolism of norepinephrine in isolated canine saphenous veins.

1. The effects S-11701 ([morpholinyl-2)-methoxy]-8-tetrahydro-1,2,3,4 quinoline) on accumulation, overflow and metabolism of [3H]norepinephrine were investigated in isolated canine saphenous veins. 2. Saphenous veins were incubated with [3H]norepinephrine in the absence or the presence of S-11701; the drug caused a concentration-dependent inhibition of the tissue content of [3H]norepinephrine and its metabolites, except for 3-methoxy-4-hydroxymandelic acid (VMA). 3. In helical strips of canine saphenous veins previously incubated with [3H]norepinephrine and then suspended for isometric tension recording and measurement of the overflow of labelled transmitter and its metabolites, S-11701 (30 microM) significantly increased the spontaneous efflux of total 3H; this effect was almost exclusively due to an augmentation of the efflux of [3H]DOPEG. 4. During electrical stimulation (9 V, 1 Hz), S-11701 at 1 microM slightly increased the overflow of extraneuronal norepinephrine metabolites without affecting the contractile response. At the higher concentration (30 microM) the compound increased the contractive response and the overflow of 3H; the latter was due mainly to an increase in [3H]DOPEG and, to a lesser extent, in [3H]norepinephrine. 5. DMI (1 microM) did not interfere with the effects of S-11701 on DOPEG efflux. 6. These experiments indicate that in the canine saphenous vein, S-11701 causes a concentration-dependent inhibition of neuronal accumulation of [3H]norepinephrine. At higher concentrations, S-11701 enters the adrenergic nerve terminals independently of the neuronal amine carrier and displaces [3H]norepinephrine from its storage sites.

Animals↗

PubMed1995

Norepinephrine modulates high voltage-activated calcium channels in freshly dissociated rat nucleus tractus solitarii neurons.

The effects of norepinephrine on the low- and high-voltage-activated calcium channels in the neurons acutely dissociated from the nucleus tractus solitarius of 2- to 3-week-old rats were investigated in the nystatin perforated patch recording configuration under voltage-clamp conditions. The norepinephrine had no effect on the low voltage-activated calcium channel but inhibited the high voltage-activated calcium channel in a concentration-, time- and voltage-dependent manner. The norepinephrine slowed the activation phase of the high voltage-activated calcium channel current and the maximum inhibition was 30% of the total current amplitude measured 10 ms after the current activation. The inhibitory effect was eliminated by applying larger depolarizing prepulses. The pretreatment with pertussis toxin completely blocked the norepinephrine effect on high-voltage activated calcium channels, suggesting the contribution of pertussis toxin-sensitive Gi/Go-proteins to the norepinephrine-induced inhibition. Yohimbine but not prazosin nor propranolol antagonized the norepinephrine-induced inhibition, suggesting the involvement of alpha 2-adrenoceptor in norepinephrine-induced inhibition of the high voltage-activated calcium channels. omega-Conotoxin-GVIA, omega-agatoxin-IVA, nicardipine and omega-conotoxin-MVIIC blocked the high voltage-activated calcium channel current by 26, 9, 36 and 11% of the total current respectively, suggesting the existence of N-, P-, L- and Q-type calcium channels in the nucleus tractus solitarii neurons. The current being insensitive to these calcium channel antagonists, termed R-type calcium channel current, also existed. This residual R-type calcium channel was completely blocked by adding 200 microM CD2+. The norepinephrine significantly inhibited N- and P-type calcium channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Norepinephrine-mediated protein phosphorylation in astrocytes.

Studies were conducted to determine if norepinephrine activates both protein kinase C and the cyclic AMP-dependent protein kinase in cultured rat astrocytes using phosphoproteins as markers. Norepinephrine was found to decrease 32P incorporation into an acidic 80,000 M(R) protein. A similar response was observed with isoproterenol and cyclic AMP analogs. In contrast, phorbol myristate acetate (PMA) increased 32P incorporation into this protein. Further studies looked at phosphorylation sites on glial fibrillary acidic protein and vimentin using two-dimensional tryptic phosphopeptide maps. The pattern of phosphorylation of these two proteins by norepinephrine resembles that of 8-bromo cyclic AMP and isoproterenol, and not that of PMA. Additionally, the effect of norepinephrine on the phosphorylation of GFAP and vimentin was blocked by alprenolol. One difference noted between norepinephrine and isoproterenol was the phosphorylation of an 18,000 M(R) protein. Norepinephrine increased, and isoproterenol decreased, 32P incorporation into this protein; however, the mechanism which mediates the norepinephrine effect remains to be determined. Overall, these studies indicate that the most prominent phosphorylation events mediated by norepinephrine are the consequence of the activation of cyclic AMP-dependent protein kinase.

Animals↗

PubMed2005

Renal norepinephrine spillover during infusion of nonesterified fatty acids.

BACKGROUND: Sympathetic activity and renal norepinephrine spillover are increased in obese individuals. We have reported that infusion of nonesterified fatty acids increases blood pressure in animals through stimulation of the sympathetic nervous system. METHODS: In this study, we assessed the effect of increasing circulating nonesterified fatty acids on systemic and renal norepinephrine kinetics in healthy adults by infusing fat emulsion and heparin for 4 h. (3)H-norepinephrine was infused for 60 min before and again during the last hour of the fatty acid infusion to assess norepinephrine kinetics. Renal venous blood samples were obtained to calculate renal norepinephrine spillover. RESULTS: Nonesterified fatty acid levels increased threefold during the first hour and remained elevated throughout the study. Arterial and renal venous plasma norepinephrine levels fell by 15% and 20%, respectively, during the infusion (P < .05 for both). Kinetic analysis indicated that systemic release of norepinephrine into an extravascular compartment decreased from 11.6 +/- 1.1 to 10.0 +/- 1.3 nmol/min/m(2) (P = .067) and renal venous norepinephrine spillover decreased from 454 +/- 54 pmol/min (P = .055). CONCLUSIONS: These results indicate that nonesterified fatty acids do not have a direct stimulating effect on whole-body or renal sympathetic activity. It is possible that increased plasma levels of fatty acids serve as a signal to decrease sympathetic tone during the fasting state.

Adult↗

PubMed2006

The effects of norepinephrine transporter inactivation on locomotor activity in mice.

BACKGROUND: Acute administration of different classes of antidepressants can enhance or reduce spontaneous locomotor activity in a novel environment, but the effects of chronic antidepressant treatment on spontaneous locomotor activity in novel and familiar environments are less well characterized. Because norepinephrine is an important regulator of spontaneous locomotor activity, we speculated that norepinephrine transporter blockade contributes to the effects of some antidepressants on spontaneous locomotor activity. METHODS: Antidepressant drugs (reboxetine, desipramine, imipramine, venlafaxine, bupropion) were administered acutely (intraperitoneal) or chronically (via osmotic minipump) to control and norepinephrine transporter knockout mice, and spontaneous locomotor activity in novel or familiar environments was recorded. RESULTS: Acute treatment with most norepinephrine transporter-blocking antidepressants decreased spontaneous locomotor activity in a novel environment, whereas chronic treatment decreased spontaneous locomotor activity in both novel and familiar environments. The exception was bupropion, a dual norepinephrine transporter/dopamine transporter blocker, which tended to increase spontaneous locomotor activity. Coadministration of reboxetine and the dopamine transporter blocker GBR 12909 also increased spontaneous locomotor activity. Norepinephrine transporter knockout mice had low basal spontaneous locomotor activity, which was increased by bupropion, whereas reboxetine had no effect in norepinephrine transporter knockout mice. CONCLUSIONS: Acute or chronic inactivation of the norepinephrine transporter decreases spontaneous locomotor activity in novel and familiar environments unless coupled with dopamine transporter blockade.

Animals↗

PubMed1996

Production of Shiga-like toxins by Escherichia coli O157:H7 can be influenced by the neuroendocrine hormone norepinephrine.

To examine whether the neuroendocrine hormone norepinephrine may influence the production of the Shiga-like toxins (SLTs), several Escherichia coli O157:H7 clinical isolates were grown in the presence or absence of norepinephrine. An in vitro culture system consisting of low (<1500 colony-forming units/ml) initial concentrations of inocula into a serum-based medium was used to more closely approximate in vivo conditions. The growth of all isolates was increased several logs in the presence of norepinephrine, as compared with the growth in controls, during a 24-hour growth period. Controls included additional dextrose as well as the use of the norepinephrine metabolite normetanephrine, which contains one more methyl group than norepinephrine and hence would serve as a better energy source for growth if the effect were solely nutritionally mediated. During the 24 hours of growth, the production of cell-associated SLT-I on a protein-equivalent basis was shown to be increased over 100-fold in norepinephrine-cultured bacteria as compared with controls. SLT-II elaboration into culture supernatants was also greatly increased in norepinephrine-cultured bacteria as compared with controls. Maximal detection of cell-associated SLT-II occurred at least 12 hours before maximum levels were achieved in culture supernatants. Because norepinephrine represents one of the largest pools of monoamines present throughout the small intestine, these results suggest that the neuroendocrine environment of the small intestine may play a role in the growth of O157:H7 and the production of SLTs.

Bacterial Toxins↗

PubMed1990

Determination of norepinephrine levels in the adult human prostate.

Tissue levels of norepinephrine were measured in prostate tissue from 24 men ranging in age between 41 and 83 years. Prostatic tissue was obtained from men with subtle palpable prostate nodules undergoing transperineal needle biopsy. None of the patients were shown to have histologic evidence of adenocarcinoma. The severity of the symptoms of prostatism was evaluated prospectively using a standardized micturition symptom score questionnaire. Norepinephrine levels were quantified using a sensitive radioenzymatic assay (REA). Overall, the prostates contained relatively high levels of norepinephrine (1666 +/- 124 ng./gm.). Inverse correlations were observed between tissue norepinephrine levels and severity of symptoms of prostatism (r = -0.58; p = 0.003); age (r = -0.53; p = .008); and prostate size (r = -0.48; p = .02). Norepinephrine levels were also measured in tissue specimens obtained from men undergoing enucleation prostatectomy and transurethral resection of the prostate (TURP). The level of norepinephrine in these prostatectomy specimens (115 ng./gm.) was only 14% the level of the prostate biopsy specimens. The relatively low level of norepinephrine in the specimens obtained from patients with symptoms necessitating prostatectomy provides further evidence that norepinephrine levels are inversely related to the degree of symptomatic bladder outlet obstruction.

Adult↗

PubMed1997

GABA augments basal and electrically stimulated 3H-norepinephrine release in hypothalamic, preoptic area and cortical slices of female rats.

These studies examined the regulation by GABA of norepinephrine release from hypothalamus, preoptic area and frontal cortex. Using superfused brain slices from female rats, we show that 100 microM GABA enhances both basal and electrically stimulated release of 3H-norepinephrine in all three brain regions. The GABAA agonist muscimol (100 microM) significantly augments 3H-norepinephrine release, but it is somewhat less effective than GABA. The GABAB agonist baclofen has little or no effect on basal 3H-norepinephrine efflux. GABA also augments both the magnitude and duration of electrically evoked 3H-norepinephrine release in slices from all three brain regions. GABA facilitation of electrically stimulated 3H-norepinephrine release is mediated through GABAA receptors as evidenced by its blockade by 10 microM bicuculline, a GABAA antagonist, but not by 200 microM 2-OH-saclofen, a GABAB antagonist. These data show that the inhibitory amino acid neurotransmitter GABA enhances both basal and evoked release of 3H-norepinephrine in brain slices from female rats. These effects are predominantly mediated by GABAA receptors. GABA modulation of hypothalamic norepinephrine release may play a role in the regulation of gonadotropin secretion and reproductive behaviors such as lordosis.

Animals↗

PubMed2001

Rate-independent inhibition by norepinephrine of 5-HT release from the somadendritic region of serotonergic neurons.

Endogenous adrenergic drive regulates the firing rate of serotonergic neurons. However, advocates of feedback theory assert that 5-hydroxytryptamine (5-HT) released in the somatodendritic region of raphe neurons regulates both rate and release of 5-HT. Experiments were done to determine if the somatodendritic region might have receptors for norepinephrine that inhibit release of 5-HT independently of rate, as this would allow for discrete effects of norepinephrine on rate and release, even in the presence of functional feedback by 5-HT. The release of 5-HT at fixed frequencies of stimulation was substantially reduced when norepinephrine (1 and 3 x 10(-7) M) was present. Norepinephrine also inhibited the release of 3H-5-HT with delivery of a single stimulation pulse ruling out a remote action of the catecholamine. The alpha(1) antagonist prazosin did not modify the profile of norepinephrine inhibition. Further, the alpha(1) agonist phenylephrine had no effect on 3H-5-HT efflux. The alpha(2) antagonist yohimbine antagonized almost entirely the inhibition by norepinephrine at 1 Hz, and reduced it substantially at 3 Hz. Blockade of 5-HT(1) receptor sites with methiothepin did not reduce the inhibitory effect of norepinephrine on 3H-5-HT efflux. It is proposed that release of endogenous norepinephrine at synapses with 5-HT neurons could activate 5-HT neuron firing rate through alpha(1) receptors located at the soma and simultaneously short-circuit ongoing 5-HT feedback inhibition by inhibiting release through adrenergic alpha two receptors likely located at the dendrites.

Adrenergic alpha-Agonists↗

PubMed1986

Myocardial norepinephrine, epinephrine and dopamine concentrations after cardiac autotransplantation in dogs.

Myocardial norepinephrine is markedly reduced after cardiac transplantation because of interruption of postganglionic cardiac sympathetic nerves. There are also substantial stores of dopamine in the myocardium, but the influence of cardiac denervation on dopamine remains unknown. The effect of cardiac transplantation was determined and, thus, the effect of denervation on myocardial norepinephrine, dopamine and epinephrine. Myocardial catecholamines were measured with high-performance liquid chromatography with electrochemical detection in five dogs 6 to 8 weeks and in four dogs 8 to 12 years after cardiac autotransplantation and in six sham-operated dogs with intact cardiac innervation. Norepinephrine, dopamine and epinephrine levels were determined from samples obtained from the right and left atria and ventricles. Samples from the left ventricular apex and base were analyzed separately. There was a striking depletion of norepinephrine in all cardiac chambers after short-term autotransplantation. The norepinephrine content of the left atrium in sham-operated dogs (1,659 +/- 219 ng/g) was significantly higher than that of dogs with long-term autotransplanted hearts (754 +/- 372 ng/g). Sham-operated dogs and dogs with long-term autotransplanted hearts had statistically significant (p less than 0.05) differences in norepinephrine content in the left ventricular apex (480 +/- 197 versus 294 +/- 198 ng/g), left ventricular base (876 +/- 2204 versus 654 +/- 156 ng/g) and right ventricle (766 +/- 133 versus 247 +/- 29 ng/g). In contrast to norepinephrine, dopamine concentrations were relatively preserved in the short-term group despite the virtual depletion of myocardial norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum Oxide↗

PubMed1981

Norepinephrine release in essential hypertension.

Supine basal plasma norepinephrine was higher in a group of newly diagnosed patients with mild essential hypertension than in age- and sex-matched "laboratory-naive" volunteers. Sympathetic activation by exercise and change of posture increased plasma norepinephrine in both groups, with a tendency toward higher values in the hypertensive patients, but norepinephrine clearance was slower and half-life longer in these patients. Thus the estimate of neuronal norepinephrine release obtained by correction of plasma norepinephrine for individual values of clearance was in the same range in both groups. Plasma norepinephrine was lower in younger "laboratory-adapted" subjects than in the "laboratory-naive" normotensive subjects, but clearance was in the same range in both. Thus, variations in kinetics may contribute to differences in plasma norepinephrine between patients with essential hypertension and matched controls. In contrast, the lower plasma concentration of norepinephrine in "laboratory-adapted" than in "laboratory-naive" controls appears to reflect a lower level of sympathetic activity in the former.

Adult↗

PubMed1983

Effects of ethanol on plasma catecholamines and norepinephrine clearance.

Plasma catecholamines were measured in nine men after they had drunk either 0.5 or 1 ml/kg ethanol. Ethanol was found to induce a dose-dependent rise in plasma norepinephrine concentrations. Epinephrine concentrations were also raised in the initial intoxication phase. To determine whether ethanol raises plasma norepinephrine through increased release or decreased clearance (Cl), we infused norepinephrine into eight male subjects with and without prior ethanol, each subject acting as his own control. During infusions after ethanol, norepinephrine concentrations rose higher, and the mean circulatory Cl of norepinephrine was reduced from 76 to 47 ml/kg/min. This was associated with a prolongation of norepinephrine t 1/2 from 1.7 to 2.05 min. No significant difference in circulatory input of norepinephrine was found between infusions with and without ethanol. These results indicate that ethanol consumption increases plasma norepinephrine by reducing its circulatory Cl.

Adult↗

PubMed1998

Post- and presynaptic effects of norepinephrine in guinea-pig colonic submucous plexus.

Intracellular recording techniques were used to investigate the effects of norepinephrine on submucous neurones in the guinea-pig distal colon. In 81% of the neurones, pressure microejection of norepinephrine produced a membrane hyperpolarization associated with a decrease in excitability and input resistance. Microejection of clonidine (1 microM) mimicked the norepinephrine-induced hyperpolarization, whereas both phentolamine (1 microM) and yohimbine (1 microM) reversibly suppressed it. Superfusion of norepinephrine (1 nM - 10 microM) hyperpolarized the cells in a concentration-dependent manner. Norepinephrine and clonidine (1 nM - 10 microM) caused a concentration-dependent presynaptic inhibition of stimulus-evoked cholinergic fast excitatory postsynaptic potential. Slow inhibitory post-synaptic potentials (sISPSs) were induced by focal electrical stimulation of the interganglionic fibre tracts in 43% of the neurones tested. Superfusion of both phentolamine (1 microM) and yohimbine (1 microM) reduced the sIPSPs while prazosin (1 microM) had no significant effect. We concluded that norepinephrine acted post- and presynaptically via alpha 2-adrenoreceptors to have an inhibitory effect on the guinea-pig colonic submucous. In addition, our study strongly supported the role of norepinephrine as a mediator of the sIPSPs. As a result, norepinephrine would primarily suppress information transfer within the neuronal circuits in guinea-pig colonic submucosal plexus.

Acetylcholine↗