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D I Wallis

Publications and source records attributed to D I Wallis.

At least 37 records · Page 2Linked to original sources
PubMed1988

The depolarizing action of 5-hydroxytryptamine on rabbit isolated preganglionic cervical sympathetic nerves.

This study describes a depolarizing action of 5-hydroxytryptamine (5-HT) on rabbit isolated preganglionic cervical sympathetic nerves using an extracellular recording technique. From cumulative concentration-response curves for 5-HT (1 mumol/l-1 mmol/l), the mean maximal depolarization was shown to be 277 +/- 32 microV and EC50 was 9.4 mumol/l (6.5-13.6 mumol/l, geometric mean, 95% confidence limits, n = 42). The responses to 5-HT displayed marked tachyphylaxis. When cumulative concentration-response curves to 5-HT and 2-methyl-5-HT were determined in the same preparations (n = 4), the mean maximal response to 5-HT was 519 +/- 167 microV, EC50 32.2 mumol/l (8.8-118 mumol/l) and the mean maximal response to 2-methyl-5-HT was 317 +/- 63 microV, EC50 35.1 mumol/l (12.9-95.5 mumol/l, geometric means, 95% confidence limits). The action of selective 5-HT antagonists was tested on repeated cumulative concentration-response curves to 5-HT. Neither methiothepin (0.1-1 mumol/l, n = 3) nor ketanserin (0.1-1 mumol/l, n = 3) had an action on 5-HT responses. The selective 5-HT3 antagonists MDL 72222, ICS 205-930 and SDZ 206-830 were all potent antagonists of the 5-HT depolarizations. The action of these antagonists was quantified by determining the apparent pA2 from the dose ratios and a Schild plot.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

A comparison of fast and slow depolarizations evoked by 5-HT in guinea-pig coeliac ganglion cells in vitro.

1. 5-Hydroxytryptamine (5-HT) was applied by pressure ejection to coeliac ganglion cells of the guinea-pig maintained in vitro and responses measured intracellularly. 2. Cells responded in one of three ways to 5-HT: by (a) a fast, transient depolarization (43%), (b) a fast transient followed by a slow depolarization (biphasic response, 30%) or (c) a slow sustained depolarization (25%). 3. Fast depolarizations (response (a) above] were graded according to the duration of the ejection pulse. Maximal responses had a mean amplitude of 12 +/- 0.8 mV, a duration of 6.4 +/- 1.0 s, a latency of 0.4 +/- 0.1 s, were associated with a fall in membrane input resistance, increased in amplitude by hyperpolarization and probably mediated by an increased conductance to Na and K. The estimated reversal potential was -22.8 +/- 2.4 mV (n = 14). The maximal fast response seen in biphasically-responding cells (b) appeared similar to fast response (a). 4. Fast depolarizations (a) showed marked tachyphylaxis and were abolished by superfusion of the ganglion with 5-HT (100 microM). They were reduced in amplitude by tubocurarine (10-100 microM, pIC50 4.4), MDL 72222 (1-5 microM, pIC50 5.8), quipazine (1 microM reduced responses by 65 +/- 15%, n = 3), ICS 205-930 (1 microM reduced responses by 64 +/- 14%, n = 7) and metoclopramide (10 microM reduced responses by about 45%), but were unafected by methysergide (up to 1 microM) or hexamethonium (up to 1 mM). 5. Slow depolarizations (c) varied in amplitude with the duration of the ejection pulse. Maximal responses had a mean amplitude of 6.4 +/- 0.7 mV, a duration of 62 +/- 6 s, a latency of 3.5 +/- 0.8 s and were reduced in amplitude by methysergide (0.1-1 microM, pIC50 6.5) but not by MDL 72222 (1 microM). The maximal slow component in biphasically-responding cells (b) was similar in amplitude and duration to slow response (c), was partially blocked by methysergide (1-5 microM) in 4 of 6 cells and was enhanced by tubocurarine (50 microM) which reduced the fast component. 6. Slow depolarizations (b,c) were associated with either a small reduction or no change in membrane input resistance depending on the cell studied. Hyperpolarization had variable effects on slow depolarization amplitude. 7. It was concluded that the fast, phasic depolarization is mediated by an ionic mechanism and by receptors both of which are distinct from those involved in the slow depolarization. The receptor mediating the fast depolarization is a 5-HT3 receptor while that mediating the slow depolarization has yet to be identified.

Animals↗
PubMed1988

Responses to 5-hydroxytryptamine evoked in the hemisected spinal cord of the neonate rat.

1. Superfusion of isolated hemisected spinal cord from neonate rats with 5-hydroxytryptamine (5-HT) (10(-6) to 10(-3) M) evoked concentration-related depolarizations. The maximal depolarization elicited by a concentration of 10(-4) M was 1.0 +/- 0.1 mV (mean +/- s.e.mean, n = 30). Noradrenaline in a similar range of concentrations also elicited depolarizations. 2. The depolarizations probably originate in motoneurones as a result of direct interaction of the amines with these cells, since responses were unaltered by tetrodotoxin (10(-7) M) or Ca2+-free/Mg2+-rich medium. 3. 5-Carboxamidotryptamine (5-CT), S(+)-alpha-methyl-5-hydroxytryptamine (alpha-Me5-HT) and 5-methoxytryptamine (5-MeOT) evoked similar depolarizations to 5-HT. Tryptamine evoked depolarizations of smaller maximal amplitude. 5-Hydroxytryptophan, 2-methyl-5-hydroxytryptamine, 8-hydroxy-2-(di-N-propylamino) tetralin hydrobromide (8-OH-DPAT) and 5-methoxy-3-[1,2,3,6-tetrahydro-4-pyridinyl]-1-H-indole succinate (RU 24969) had no depolarizing action. 4. Concentration-response (CR) curves were determined for 5-HT, 5-CT, alpha-Me5-HT, 5-MeOT and tryptamine. The ED50 value for 5-HT was 20.5 +/- 1.2 microM. The equipotent molar ratios (EPMRs) for 5-CT and alpha-Me5-HT were close to unity, while 5-MeOT was approximately 3 times and tryptamine 13 to 14 times less potent than 5-HT. 5. The relative agonist potency of 5-HT with respect to other tryptamine analogues capable of depolarizing motoneurones was increased when 5-HT uptake was blocked by citalopram (10(-7) M). In the presence of citalopram, 5-HT was 2.7 times more potent than alpha-Me5-HT and 16.9 times more potent than 5-CT. The apparent order of potency was 5-HT greater than alpha-Me5-HT greater than 5-CT (greater than 5-MeOT much greater than tryptamine). 6. The monoamine oxidase inhibitor, pargyline (5 x 10(-4) M), had no effect on depolarizations to 5-HT, 5-CT or alpha-Me5-HT. 7. Methiothepin, 1 alpha H, 3 alpha, 5H-tropan-3-yl-3,5-dichlorobenzoate methanesulphonate (MDL 72222) and [3 alpha-tropanyl]-1H-indole-3-carboxylic acid ester hydrochloride (ICS 205-930) had no effect on 5-HT depolarizations elicited in motoneurones. Ketanserin (0.75 x 10(-7) M to 10(-6) M) showed modest antagonistic action and depressed maximal response amplitude; the pIC50 was 6.5. 8. Methysergide (10-8 to 10- 7M) was a potent antagonist of responses to 5-HT. CR curves were displaced to the right and flattened in the presence of the antagonist. The pIC5o assessed from the effect on depolarizations evoked by 5-HT 1O-4M was 7.5. 9. It is concluded that 5-HT acts directly to depolarize mammalian spinal motoneurones through receptors that are also activated by 5-CT, alpha-MeS-HT and 5-MeOT and are blocked by methysergide. The receptor profile, although not 5-HT3-like, does not clearly coincide with that for either 5-HT1-like or 5-HT2 receptors.

Animals↗
PubMed1988

An electrophysiological study of ganglion blockade by paraquat and diquat.

1. The bipyridilium herbicides, particularly paraquat, have chemical and toxicological features in common with the bi-quaternary ammonium ganglion blockers. 2. Paraquat and diquat were tested for ganglion blocking activity. Rabbit cervical ganglia were superfused with both agents and subsequently with hexamethonium to confirm susceptibility to ganglion blockade. 3. No evidence for ganglion blockade was found at either supra maximal or sub maximal stimulation, and none following repetitive stimulation. 4. The similarities and differences between the bipyridyl herbicides and bi-quaternary ganglion blockers can be explained on the basis of their structures. 5. It is concluded that neither paraquat nor diquat have significant ganglion blocking activity.

Animals↗
PubMed1987

Further studies on the blockade of 5-HT depolarizations of rabbit vagal afferent and sympathetic ganglion cells by MDL 72222 and other antagonists.

The blocking action of MDL 72222 (1 alpha H, 3 alpha, 5 alpha H-tropan-3-yl-3, 5-dichlorobenzoate at 5-hydroxytryptamine (5-HT) receptors on nodose (NG) and superior cervical ganglia (SCG) has been investigated further. The sucrose-gap technique was used to record potential changes from populations of neurones. The surmountable blockade induced by small concentrations of the antagonist was quantified and the blocking potency compared with that of a number of other compounds. In nodose ganglia three 4-5 point dose-response (DR) curves were established, using bolus injections of 5-HT (5-80 nmol). The mean amplitude of the response to 80 nmol was 4.18 +/- 0.53 mV and the ED50 was 18.2 nmol. Second and 3rd dose-response curves showed small displacements to the right, indicating a slight reduction in sensitivity. In superior cervical ganglia responsiveness was less. Amounts of 5-HT ranging from 20 to 320 nmol evoked dose-related depolarizations. The mean amplitude of the response evoked by 320 nmol 5-HT was 1.7 +/- 0.14 mV. Three 4-5 point dose-response curves could be elicited from a single ganglion. The ED50 was 55.8 nmol. Initial, 2nd and 3rd dose-response curves could be superimposed, there being no significant rightward shift. The results confirm that MDL 72222 is a potent, selective antagonist at 5-HT receptors in nodose and superior cervical ganglia. In the nodose ganglion, after equilibration for 1 hr with 10(-8) or 10(-7) M MDL 72222, dose-response curves for 5-HT showed rightward, parallel shifts. In contrast, 10(-6) M MDL 72222 or prolonged exposure (3-4 hr) to 10(-8), 10(-7) or 10(-6) M caused larger rightward shifts of the dose-response curves and depressed the maximum responses. In the superior cervical ganglion, equilibration for 1 hr with concentrations of 10(-8) or 10(-7) M produced effects on the dose-response curves similar to those seen in the nodose ganglion, but longer exposures (3-4 hr) did not depress the maximum. Apparent pA2 values were determined from individual experiments on both the nodose and superior cervical ganglia, where MDL 72222 (10(-7) M or less, for 1 hr) caused parallel or near parallel shifts of dose-response curves. In the nodose ganglion the apparent pA2 was 7.7 +/- 0.1, while in the superior cervical ganglion it was 7.8 +/- 0.1 (mean +/- SEM). The nature of the blockade induced by prolonged exposures or by concentrations greater than 10(-7) M is discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

Fast and slow depolarizing responses of guinea-pig coeliac ganglion cells to 5-hydroxytryptamine.

Responses to 5-hydroxytryptamine (5-HT) applied by pressure ejection to guinea-pig coeliac ganglion cells were recorded intracellularly in vitro. Three types of responses were observed: a fast depolarization (43% of cells), a slow depolarization (25%) and a biphasic response comprising an initial fast followed by a slow depolarization (30%). Fast depolarizations had a mean duration of 6.4 s and were associated with a decrease in membrane input resistance. On hyperpolarizing the membrane, responses increased in amplitude; the mean reversal potential was -23 mV. Fast responses were nearly eliminated in a Na-free medium but were unaffected by low Ca/high Mg solution or by low Cl medium. Fast responses were depressed by MDL 72222, quipazine, metoclopramide, and by relatively high concentrations of D-tubocurarine, but unaffected by methysergide. Slow responses had a mean duration of 62 s and were associated either with no change or a slight fall in membrane resistance. hyperpolarizing the membrane, slow responses were increased in most but not all cells tested. Slow depolarizations were depressed by methysergide but unaffected by agents that suppressed the fast responses. The biphasic response displayed electrophysiological and pharmacological characteristics of both the fast and slow depolarizations. It is concluded that guinea-pig coeliac ganglion cells display either a rapid depolarization, a slow depolarization or a biphasic response to 5-HT, that the fast depolarization appears to be mediated by a conductance increase to Na and K, while a different mechanism appears to underlie the slow depolarization, and that the two responses are mediated by different kinds of 5-HT receptor.

Animals↗
PubMed1986

The depolarizing action of 5-hydroxytryptamine on rabbit vagal afferent and sympathetic neurones in vitro and its selective blockade by ICS 205-930.

Depolarizing responses to 5-hydroxytryptamine (5-HT) were recorded from rabbit nodose (NG) and superior cervical (SCG) ganglia using the sucrose-gap technique. The antagonist potency and selectivity of ICS 205-930 ([3 alpha-tropanyl]-1H-indole-3-carboxylic acid ester) were investigated. In NG, 5-HT (5 to 80 nmol) evoked depolarizations of graded amplitude. The ED50 was 18.2 (10.9-30.5) nmol (geometric mean, 95% confidence limits). Responses were blocked surmountably by ICS 205-930, 10(-11) and 10(-10) M, the threshold for blockade being below 10(-11) M. Parallel, rightward shifts in dose-response curves were seen with these concentrations of antagonist, but at higher concentrations (10(-9) and 10(-8) M) there was a further rightward shift with reduction in slope and maximum of the curves. In SCG, where 5-HT (20 to 320 nmol) evoked depolarizations of graded amplitude and the ED50 was 55.8 (22.3-139.6) nmol (geometric mean, 95% confidence limits), ICS 205-930 had a similar inhibitory effect to that observed in NG. The apparent pA2 values for the surmountable blockade produced by ICS 205-930 at concentrations of 10(-11) and 10(-10) M were 10.2 +/- 0.2 for NG and 10.4 +/- 0.1 for SCG (means +/- s.e. mean). ICS 205-930 was selective in its action since it had no effect on dimethylphenylpiperazinium (DMPP) responses in either ganglion or on GABA responses in NG. This study provides quantitative evidence on the blocking action of ICS 205-930 at neuronal 5-HT receptors using a technique that allows the depolarizing responses evoked by the amine to be directly recorded.

Animals↗
PubMed1985

The depolarizing action of 5-hydroxytryptamine on rabbit vagal primary afferent and sympathetic neurones and its selective blockade by MDL 72222.

MDL 72222 (1 alpha H,3 alpha,5 alpha H-tropan-3-yl-3,5-dichlorobenzoate) is a novel compound with potent and selective blocking actions at certain excitatory 5-hydroxytryptamine (5-HT) receptors on mammalian peripheral neurones. In the present study, the sucrose-gap technique has been used to record depolarizing responses to 5-HT from the cells of the rabbit nodose and superior cervical ganglia and to investigate the potency and selectivity of MDL 72222 as an antagonist of these responses. On nodose ganglia, responses to 5-HT were inhibited surmountably by MDL 72222 at concentrations up to 100 nmol/l. The threshold for antagonism was 2-10 nmol/l and the apparent pA2 value (Schild 1947) was 7.7 +/- 0.2, n = 10. Blockade was selective since responses to GABA and noradrenaline were unaffected by MDL 72222, 100 nmol/l. With concentrations of MDL 72222 higher than 100 nmol/l, antagonism was concentration-related but not in a manner consistent with simple competitive antagonism and even a concentration of 1 mumol/l failed to abolish the response to 5-HT. The results from the superior cervical ganglion were essentially similar to those obtained from the nodose ganglion. The threshold concentration of MDL 72222 for inhibition of 5-HT was 1-10 nmol/l and blockade was selective in that depolarizing responses to dimethylphenyl-piperazinium (DMPP) was unaffected by a concentration of MDL 72222 of 1 mumol/l. The data provide direct evidence that MDL 72222 is a potent and selective antagonist of the receptors for 5-HT which mediate depolarizing responses in vagal primary afferent cell bodies and in sympathetic ganglion cells.

Animals↗
PubMed1985

Properties of visceral primary afferent neurons in the nodose ganglion of the rabbit.

The active and passive membrane properties of rabbit nodose ganglion cells and their responsiveness to depolarizing agents have been examined in vitro. Neurons with an axonal conduction velocity of less than 3 m/s were classified as C-cells and the remainder as A-cells. Mean axonal conduction velocities of A- and C-cells were 16.4 m/s and 0.99 m/s, respectively. A-cells had action potentials of brief duration (1.16 ms), high rate of rise (385 V/s), an overshoot of 23 mV, and relatively high spike following frequency (SFF). C-cells typically had action potentials with a "humped" configuration (duration 2.51 ms), lower rate of rise (255 V/s), an overshoot of 28.6 mV, an after potential of longer duration than A-cells, and relatively low SFF. Eight of 15 A-cells whose axons conducted at less than 10 m/s had action potentials of longer duration with a humped configuration; these were termed Ah-cells. They formed about 10% of cells whose axons conducted above 2.5 m/s. The soma action potential of A-cells was blocked by tetrodotoxin (TTX), but that of 6/11 C-cells was unaffected by TTX. Typically, A-cells showed strong delayed (outward) rectification on passage of depolarizing current through the soma membrane and time-dependent (inward) rectification on inward current passage. Input resistance was thus highly sensitive to membrane potential close to rest. In C-cells, delayed rectification was not marked, and slight time-dependent rectification occurred in only 3 of 25 cells; I/V curves were normally linear over the range: resting potential to 40 mV more negative. Data on Ah-cells were incomplete, but in our sample of eight cells time-dependent rectification was absent or mild. C-cells had a higher input resistance and a higher neuronal capacitance than A-cells. In a proportion of A-cells, RN was low at resting potential (5 M omega) but increased as the membrane was hyperpolarized by a few millivolts. A-cells were depolarized by GABA but were normally unaffected by 5-HT or DMPP. C-cells were depolarized by GABA in a similar manner to A-cells but also responded strongly to 5-HT; 53/66 gave a depolarizing response, and 3/66, a hyperpolarizing response. Of C-cells, 75% gave a depolarizing response to DMPP.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

5-HT antagonists and blockade of neuronal (5-HT) receptors on ganglion cells.

Potential changes in superior cervical ganglion cells evoked by 5-HT or the nicotinic agonist, dimethyl-phenyl piperazinium (DMPP), were recorded using the sucrose-gap method and a number of putative 5-HT antagonists tested for potency and selectivity. Selective blockade of 5-HT responses was produced by 5-HT itself and, in increasing order of potency, by cocaine, metoclopramide and quipazine. A non-selective blockade was observed with bufotenine and d-tubocurarine. Substances which had no effect on 5-HT responses included methysergide and other compounds related to LSD, cinanserin, cyproheptadine, phenylbiguanide and morphine. The results provide further information about the 5-HT receptor on sympathetic ganglion cells and support the view that this receptor is distinct from neuronal receptors in the myenteric plexus and on cholinergic nerve terminals.

Acetamides↗
PubMed1984

Generation of an unusual depolarizing response in rabbit primary afferent neurones in the absence of divalent cations.

The effects of divalent cations on responses to 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA) and 1,1-dimethyl-4-phenyl piperazinium (DMPP) were investigated using a sucrose-gap method to record population responses. In Ca-free medium responses to 5-HT were enhanced, those to DMPP depressed and those to GABA unchanged. In Mg-free medium responses to 5-HT were unchanged, while those to DMPP and GABA were depressed. Removal of both Ca and Mg from the superfusion medium caused a small reduction of GABA responses and a large reduction of DMPP responses. Responses to 5-HT were not only greatly potentiated but were changed in character; the depolarizing phase became sigmoid and the dose dependence between quantity of 5-HT and response magnitude was lost as if 5-HT were triggering an all-or-nothing phenomenon. Dose--response relationships for GABA were normal in the large majority of preparations. In about 10% of preparations, supramaximal amounts of GABA or DMPP evoked large responses of a similar character to those evoked by 5-HT. The large responses, generated by an unknown mechanism, were termed X responses. Further reduction in tissue divalent cations by EGTA (1 mM) caused X responses to be generated spontaneously. Ca, Mg, Mn or Co (1 mM) could suppress X responses. DMPP responses, reduced in Ca/Mg-free medium, were largely restored by 1 mM-Ca. Depression of GABA responses in Ca/Mg-free medium could be entirely attributed to the absence of Mg, Mn being able to substitute for Mg. X responses were generated only after equilibration for 1 h with Ca/Mg-free medium. Attempts to manipulate [Ca]i with dinitrophenol or caffeine did not produce the conditions under which X responses were generated. Intracellular records of responses to 5-HT, GABA or DMPP showed that cells with A fibres responded to GABA but not to 5-HT or DMPP. Fifty-four out of sixty-seven cells with C fibre axons (80%) were depolarized by 5-HT, thirty-seven out of forty-nine (76%) by DMPP and forty out of fifty-seven (70%) by GABA. Eighteen out of thirty-eight (47%) C cells were depolarized by all three agents. Some C cells were very sensitive to 5-HT, 10(-6) M evoking a substantial response. In most, responses to 10(-5) M-5-HT had a slower rate of rise than responses to 10(-4) or 10(-3) M-GABA or DMPP, yet lower 5-HT concentrations normally elicited X responses in sucrose-gap experiments whereas GABA or DMPP normally did not.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1982

Depolarizing responses recorded from nodose ganglion cells of the rabbit evoked by 5-hydroxytryptamine and other substances.

Membrane potential changes induced by 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA) and 1,1-dimethyl-4-phenyl piperazinium (DMPP) were recorded from nodose ganglia (NG) by the sucrose-gap method. An amount of 0.002-0.5 mumol of the depolarizing agent was injected into the superfusion stream to the ganglion. Responses to 5-HT were also evoked from superior cervical (SCG) and dorsal root ganglia (DRG). 5-Hydroxytryptamine elicited depolarizations of graded amplitude. Maximal responses were 4.5 +/- 0.4 mV in nodose ganglia compared to 2.2 +/- 0.2 mV in superior cervical and 0.6 +/- 0.1 mV in dorsal root ganglia (means +/- SEM). In nodose ganglia, GABA induced smaller maximal depolarizations than did 5-HT, similar to those evoked by DMPP; dopamine was a weak depolarizing agent while substance P was apparently inactive. The dose-response curve for 5-HT in nodose ganglia was parallel to that for 5-HT in superior cervical ganglia and significantly to the left (ED50 values 0.029 and 0.098 mumol). Curves for 5-HT and GABA in nodose ganglia were superimposable. The high sensitivity of nodose ganglia cells to 5-HT is briefly discussed. Analogues of 5-HT lacking a hydroxyl group at position 5 on the nucleus were relatively inactive as depolarizing agents. Picrotoxin (10(-6)-10(-5) M) reduced or suppressed responses in nodose ganglia to GABA, whereas responses to 5-HT and DMPP were not much affected or, in the case of 5-HT, sometimes somewhat reduced. Quipazine (10(-6) M) was a selective antagonist of 5-HT responses in nodose ganglia; those to GABA and DMPP were not significantly altered. Neither trazodone nor LSD displayed antagonist properties at 5-HT receptors in nodose ganglia.

Animals↗
PubMed1981

Effects of divalent cations on responses of a sympathetic ganglion to 5-hydroxytryptamine and 1,1-dimethyl-4-phenyl piperazinium.

1 The effects of raising or lowering [Ca(2+)](o) or [Mg(2+)](o) on potential changes evoked by 5-hydroxytryptamine (5-HT) and by the nicotinic agonist, 1,1-dimethyl-4-phenyl piperazinium (DMPP) have been investigated.2 Changes in membrane potential were measured at the ganglion or in postganglionic axons by the sucrose-gap technique. The ganglionic response to both 5-HT and DMPP was a depolarization followed by an after-hyperpolarization (AH). AH decayed exponentially over most of its time course; the time constant of decay for 5-HT responses was 4.4 +/- 0.3 min (mean +/- s.e.mean, rate constant 0.23 min(-1)) and that for DMPP responses was not significantly different, being 3.9 +/- 0.3 min (rate constant 0.26 min(-1)).3 Increasing [Ca(2+)](o) to 5.1 or 7.6 mM caused some hyperpolarization of the ganglion, reduced the amplitude of depolarizations evoked by 5-HT by 29% and usually potentiated responses to DMPP (average 12%). Ca-free solutions caused a depolarization of the ganglion, increased the amplitude of depolarizations evoked by 5-HT by 23% and reduced that of depolarizations to DMPP by 32%. [Mg(2+)](o) 12.7 and 25.4 mM caused depolarizations of the ganglion and reduced the amplitude of depolarizations evoked by 5-HT by 34 and 84%, respectively, and those to DMPP by 10 and 75%, respectively. Mg-free solutions or low [Mg(2+)](o) caused a slow depolarization of the ganglion and reduced the amplitude of depolarizations to both 5-HT and DMPP by approx. 20%. Ca/Mg-free solutions produced a slow depolarization of the ganglion, increased the amplitude of depolarizations evoked by 5-HT by 78% and reduced those to DMPP by 58%.4 Increasing [Ca(2+)](o) reduced the amplitude of AH evoked by 5-HT by 50% and increased that to DMPP by 73%, while prolonging AH duration and increasing the time constant of decay. Ca-free solutions had complex effects on AH evoked by 5-HT, which were increased on average by 116%, and depressed AH evoked by DMPP; in both cases there was a decrease in the time constant of decay. [Mg(2+)](o) 12.7 mM reduced the amplitude of AH evoked by 5-HT more than that evoked by DMPP, and increased the rate of decline of the exponential phase. Low Mg solutions reduced in amplitude the AH evoked by 5-HT by 56% and the AH evoked by DMPP by 38%. The time constant of decay was increased. Ca/Mg-free solutions reduced AH amplitude in both 5-HT and DMPP responses. The effects on time constant are consistent with the generation of AH by an electrogenic sodium pump, the ATP-ase of which is Mg(2+)-dependent and inhibited by Ca(2+).5 Responses to 5-HT could be recorded from postganglionic axons and consisted of a rapid depolarization, sometimes followed by an AH whose time constant of decay was smaller than that of ganglionic responses. Full dose-response curves in control and test media could be obtained. In Ca/Mg-free solutions, 5-HT depolarizations were potentiated but no significant shift in the curve was observed.6 It is suggested that divalent cations modulate the coupling between 5-HT receptor and ion channel, an increase in [Ca(2+)](o) reducing the coupling or stabilizing the ion channel in the closed conformation. Ca(2+) and Mg(2+) may compete for the same binding site. This mechanism does not appear to be involved at nicotinic receptors and their related ion channels.

Animals↗
PubMed1980

Characteristics of dorsal root potentials recorded from the isolated spinal cord of the neonate rat.

Dorsal root potentials (DRP) and dorsal root reflexes (DRR) have been recorded from the isolated cord of the neonate rat. A single stimulus to the adjacent rostral or adjacent caudal dorsal root or dorsal columns evoked a DRP, the peak amplitude of which was reached in 110--115 msec and which decayed exponentially over most of its time course (time constant 800--850 msec). The same stimuli evoked field potentials in the dorsal horn comprising fast negative, slow negative and slow positive potentials. DRP had a lower threshold than DRR and reached a maximal amplitude at stimulus voltages sub-maximal for DRR. Increasing the intensity of stimulation shortened the latency of DRP and prolonged its time course. DRR and DRP were depressed by a prior conditioning stimulus (CS) and by the addition of Mg++ ions to the bathing solution. A CS was more effective in producing depression of responses evoked more rostrally than more caudally.

Animals↗
PubMed1980

Antagonism of 5-hydroxytryptamine receptors by quipazine.

1 The antagonist actions of quipazine on 5-hydroxytryptamine (5-HT) receptors have been investigated in the rabbit isolated superior cervical ganglion and on the rat isolated spinal cord and stomach strip. 2 Changes in membrane potential induced by 5-HT or by the nicotinic agonist, 1,1-dimethyl-4-phenyl piperazinium (DMPP), were measured in the ganglion by the sucrose-gap technique. At ganglionic receptors, quipazine had little or no agonist activity, but greatly depressed depolarizations evoked by 5-HT but not depolarizations evoked by DMPP or trimethylammonium (TMA). Injections into the superfusion stream to the ganglion of 2 to 5 mumol quipazine in a small volume of Krebs solution prevented all subsequent responses to 5-HT. Superfusion of the ganglion with quipazine at a concentration of 1 microM produced complete blockade of responses to 5-HT in 3 of 6 ganglia and reduced responses by over 90% in 2 others; responses to DMPP were potentiated in amplitude and duration. Superfusion at a concentration of 0.1 microM depressed responses to 5-HT by 75% on average. The threshold concentration for the blocking action was around 0.01 microM, which depressed responses by 42% on average in 6 experiments (range 0 to 75%). 3 5-HT (1 microM or 100 microM) depressed the amplitude of the dorsal root potentials recorded from the isolated, hemisected cord of the neonate rat by 27 +/- 5% (mean +/- s.e. mean, n = 14) and by 45 +/- 6% (n = 14), respectively. In the presence of quipazine (0.01 microM), 5-HT (1 microM or 100 microM) depressed the amplitude by 6 +/- 2% (n = 15) and by 3 +/- 1% (n = 7), respectively. 4 Concentration-response curves of the contractions induced by 5-HT in the fundus of the rat stomach were obtained in the absence and presence of quipazine. Quipazine (1 microM) shifted the concentration-response curve to the right and depressed the maximum, suggesting a non-competitive mode of antagonism. pI50 values were calculated in order to assess the antagonist activity of quipazine at rat fundus 5-HT receptors; the mean pI50 was 6.91 +/- 0.2 (n = 6). 5 It is concluded that quipazine may be an effective antagonist at 5-HT receptors in various tissues.

Animals↗