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K Starke

Publications and source records attributed to K Starke.

At least 19 recordsLinked to original sources
PubMed1992

Stable adenine nucleotides inhibit [3H]-noradrenaline release in rabbit brain cortex slices by direct action at presynaptic adenosine A1-receptors.

Effects of adenosine and nucleotides on the release of previously stored [3H]-noradrenaline were studied in rabbit brain cortex slices. The slices were stimulated twice, in most experiments by 6 electrical field pulses delivered at 100 Hz. Adenosine and the nucleotides AMP, ADP, ATP, AMPS, ADP beta S, ATP gamma S, beta,gamma-imido-ATP and beta,gamma-methylene-ATP all reduced the evoked overflow of tritiated compounds. For purines for which concentration-response curves were determined, the order of potency was adenosine greater than ATP approximately ATP gamma S approximately beta,gamma-imido-ATP approximately ADP greater than beta,gamma-methylene-ATP. AMP 30 mumol/l and AMPS 30 mumol/l were approximately equieffective with 30 mumol/l of adenosine and ATP gamma S, and ADP beta S 30 mumol/l was approximately equieffective with 30 mumol/l of ADP. alpha,beta-Methylene-ADP, 2-methylthio-ATP, UTP and GTP gamma S did not change the evoked overflow of tritium. alpha,beta-Methylene-ATP caused an increase; however, the increase was small and became significant only after 59 min of exposure to alpha,beta-methylene-ATP or when the slices were stimulated by 30 pulses, 10 Hz. Neither adenosine deaminase (100 U/l) nor the blocker of 5'-nucleotidase, alpha,beta-methylene-ADP (10 mumol/l), attenuated the inhibition caused by ATP, ATP gamma S and beta,gamma-methylene-ATP, despite the fact that adenosine deaminase abolished the effect of adenosine. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX, 10 nmol/l) shifted the concentration-response curves of adenosine, ATP gamma S, beta,gamma-imido-ATP and beta,gamma-methylene-ATP to the right by very similar degrees. 8-(p-Sulphophenyl)-theophylline (30 and 300 mumol/l) also markedly antagonized the inhibition produced by ATP gamma S. alpha,beta-Methylene-ATP (10 and 30 mumol/l) and suramin (100 mumol/l) did not modify the effects of adenosine, ATP gamma S and beta,gamma-methylene-ATP. It is concluded that nucleotides themselves can inhibit the release of noradrenaline in the rabbit brain cortex. The nucleotides and adenosine seem to act at the same site, i.e., the A1 subtype of the P1-purinoceptor. The results support the notion that metabolically stable, phosphate chain-modified nucleotides such as ATP gamma S, beta,gamma-imido-ATP and beta,gamma-methylene-ATP can be potent P1 agonists. No evidence was found for presynaptic P2x-, P2y- or P3-purinoceptors.

Adenine Nucleotides↗
PubMed1992

Adenosine but not an adenine nucleotide mediates tonic purinergic inhibition, as well as inhibition by glutamate, of noradrenaline release in rabbit brain cortex slices.

A possible contribution of adenine nucleotides to the endogenous purinergic, A1-receptor-mediated inhibition of noradrenaline release was studied in rabbit occipito-parietal cortex slices. The slices were preincubated with [3H]-noradrenaline and then superfused and stimulated electrically, in most experiments by trains of 6 pulses/100 Hz. A few experiments were carried out in rat occipito-parietal cortex slices. The A1-purinoceptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 1-100 nmol/l) as well as the enzyme adenosine deaminase (0.1-10 U/ml) increased the electrically evoked overflow of tritiated compounds. The maximal increase was by about 85% for both DPCPX and adenosine deaminase. The increases obtained with maximally effective concentrations of DPCPX and adenosine deaminase were not additive. The alpha 1-adrenoceptor-selective agonist methoxamine (10 but not 1 mumol/l) reduced the evoked overflow. Its effect was antagonized by yohimbine 1 mumol/l but then not attenuated further by DPCPX 100 nmol/l. L-Glutamate (300 mumol/l-2.3 mmol/l) also reduced the evoked overflow of tritium. Its effect was not changed by yohimbine 1 mumol/l but greatly, and to the same extent, attenuated by DPCPX 100 nmol/l and adenosine deaminase 3 U/ml. Neither the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine nor omission of Mg++ changed the inhibition by glutamate. Glutamate did not alter the basal efflux of tritium from rabbit cortex slices under any experimental condition. In contrast, glutamate (100 mumol/l and 1 mmol/l) caused an immediate, marked and transient acceleration of tritium outflow from rat occipitoparietal cortex slices (medium without Mg++).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1992

Pharmacological characterization of presynaptic alpha 2-autoreceptors in rat submaxillary gland and heart atrium.

1. The pharmacological properties of presynaptic alpha 2-autoreceptors were studied in rat isolated submaxillary glands and atria. Tissue pieces were preincubated with [3H]-noradrenaline, then superfused with medium containing desipramine, and stimulated electrically. In one series of experiments, pEC30 values of 12 alpha-adrenoceptor antagonists were determined, i.e., negative logarithms of concentrations that increased the electrically evoked overflow of tritium by 30%. In another series, pKD values of 9 alpha-adrenoceptor antagonists against the release-inhibiting effect of 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14304), and of 3 antagonists against the release-inhibiting effect of methoxamine, were determined. 2. In submaxillary glands, the pEC30 values of the antagonists correlated well with their pKD values against UK 14304 (r = 0.93). The same was true for atria (r = 0.92). 3. In submaxillary glands, the pKD values of 3 antagonists against UK14304 were very similar to their pKD values against methoxamine, with a maximal difference of 0.4. The same was true for atria where the maximal difference was 0.3. 4. The pEC30 values obtained in submaxillary glands correlated significantly with those obtained in atria (r = 0.81). The same was true for the pKD values (r = 0.79). However, the pEC30 and pKD values also indicated consistent differences between the two tissues. 5. It is concluded that the sites of action of the imidazoline UK 14304 (alpha 2-selective), the phenylethylamine noradrenaline, and the phenylethylamine methoxamine (alpha 1-selective) are exclusively alpha 2-adrenoceptors. There is no indication for presynaptic alpha 1-adrenoceptors or for an effect of UK 14304 mediated by presynaptic imidazoline receptors.The 02-autoreceptor population in the submaxillary gland differs from that in the atrium.6. Comparison with studies from the literature indicates that the submaxillary autoreceptors are closely similar to the a2D radioligand binding site found in the bovine pineal gland and probably the rat submaxillary gland. The atrial autoreceptors also conform best to this site, but the agreement is more limited; the atrial autoreceptors may represent a type related to, but distinct from, the a2D site, or a mixture of different types.

Adrenergic alpha-Agonists↗
PubMed1992

Effect of the dopamine D2 receptor agonist quinpirole on renal sympathetic nerve activity and renal norepinephrine spillover in anesthetized rabbits.

Cardiovascular and sympathetic nervous system effects of the dopamine D2 receptor-selective agonist quinpirole were studied in anesthetized rabbits. Sodium nitroprusside was administered for comparison. The animals received a tracer infusion of [3H] norepinephrine i.v. Arterial and renal venous concentrations of endogenous norepinephrine and epinephrine and [3H]norepinephrine, the firing rate of the renal sympathetic nerves and renal blood flow were determined. Quinpirole (100 micrograms kg-1 + 5 micrograms kg-1 min-1 i.v.) lowered blood pressure and renal vascular resistance. The firing rate of the renal sympathetic nerves was increased, but there was no reflex tachycardia. Despite the increase in renal sympathetic firing, the renal spillover of norepinephrine into blood was decreased. The increase in total body norepinephrine spillover during quinpirole-induced hypotension was less than expected from baroreflex activation. Effects of quinpirole were antagonized by domperidone (1000 micrograms kg-1 + 200 micrograms kg-1 h-1). The distinguishing feature of this study is the simultaneous measurement of sympathetic firing and norepinephrine spillover in the same organ, the kidney, under conditions of intact sympathetic impulse traffic. Quinpirole activated presynaptic D2 receptors and thus reduced the released norepinephrine per action potential. Consequences of the presynaptic inhibition were reductions of blood pressure and renal vascular resistance and absence of reflex tachycardia.

Animals↗
PubMed1992

Effects of inhibitors of neuronal uptake of 5-HT on sympathetic cardiovascular regulation.

The effect on sympathetic cardiovascular regulation of inhibition of the high-affinity neuronal uptake of 5-hydroxytryptamine (5-HT) by fluvoxamine, citalopram, and fluoxetine was studied in anesthetized rabbits. The mean arterial pressure, postganglionic renal sympathetic nerve activity, heart rate, clearance of [3H]norepinephrine from plasma and the plasma norepinephrine concentration were measured, and from the latter two parameters the spillover of norepinephrine into the blood was calculated. The effect of fluvoxamine and fluoxetine on the uptake of [3H]5-HT into platelets was also examined. Of four increasing doses of fluvoxamine (0.6, 1.7, 5, and 15 mg/kg i.v.) and citalopram (0.3, 1, 3, and 9 mg/kg i.v.), only the two highest ones decreased the renal sympathetic nerve activity, heart rate, and clearance of [3H]norepinephrine from plasma. Only the highest of four increasing doses of fluoxetine (0.2, 0.6, 1.7, and 5 mg/kg i.v.) inhibited sympathetic nerve activity. However, lower doses of fluvoxamine (0.6 and 1.7 mg/kg i.v.) and fluoxetine (0.6 and 1.7 mg/kg i.v.) already markedly inhibited the uptake of [3H]5-HT into platelets. The data indicate that selective inhibition of neuronal uptake of 5-HT has no effect on central sympathetic regulation in anesthetized rabbits. The sympathoinhibition observed at high doses of fluvoxamine and citalopram is probably due to inhibition of the neuronal uptake of norepinephrine.

Analysis of Variance↗
PubMed1992

Effect of yohimbine on renal sympathetic nerve activity and renal norepinephrine spillover in anesthetized rabbits.

The function of presynaptic alpha-2 adrenergic autoinhibition of norepinephrine release was studied in anesthetized rabbits (alfadolone + alfaxalone) with uninterrupted sympathetic impulse traffic. The animals received a tracer infusion of [3H]norepinephrine i.v. Arterial and renal venous concentrations of endogenous norepinephrine and [3H]norepinephrine, the firing rate of the renal sympathetic nerves and renal blood flow were determined. The results were used to calculate the renal fractional [3H]norepinephrine extraction, the renal removal and spillover of norepinephrine, the total body [3H]norepinephrine clearance and total body norepinephrine spillover. Sodium nitroprusside (10-80 micrograms kg-1 min-1 i.v.), which was infused to modulate sympathetic activity through the baroreceptors, caused hypotension and increased the renal sympathetic firing rate and the renal as well as total body norepinephrine spillover. Increases of total body norepinephrine spillover were much higher than increases of renal spillover. Yohimbine (1 mg kg-1 + 0.2 mg kg-1 hr-1 i.v.) caused slight central sympathoexcitation. In addition, it enhanced the renal and total body spillover of norepinephrine at any given firing rate of the renal sympathetic nerves. The distinguishing feature of this study is the measurement of sympathetic firing rate and norepinephrine spillover in one and the same organ, the kidney. The results demonstrate that the alpha-2 adrenergic autoinhibition of norepinephrine release normally operates in the kidney with intact sympathetic impulse traffic. They also suggest its operation in other peripheral sympathetically innervated tissues.

Anesthesia↗
PubMed1991

The noradrenaline uptake inhibitor, (+)-oxaprotiline, but not the inactive enantiomer, (-)-oxaprotiline, inhibits sympathetic nerve activity in the rabbit: involvement of adrenoceptors.

The effect of the enantiomers of oxaprotiline on the sympathetic nervous system was studied in anesthetized rabbits. (+)-Oxaprotile 0.2, 0.6 and 1.8 mg kg-1 dose dependently reduced prostganglionic renal sympathetic nerve activity and the clearance of [3H]noradrenaline from the plasma but increased the plasma noradrenaline concentration. The spillover of noradrenaline into the blood was not changed significantly, nor were blood pressure and heart rate, except transiently. The same doses of (-)-oxaprotiline had no effect on any of the parameters measured. (+)-Oxoprotiline also reduced lumbar preganglionic sympathetic nerve activity. The effect of (+)-oxaprotiline on renal sympathetic nerve activity was only minimally antagonized by yohimbine given alone. (+)-Oxaprotiline also inhibited renal sympathetic nerve activity after treatment with prazosin and propranolol. Subsequent administration of yohimbine restored sympathetic nerve activity to the value seen before the administration of (+)-oxaprotiline. The results show that inhibition of the re-uptake of released noradrenaline is the basis of the sympathoinhibition produced by (+)-oxaprotiline. Noradrenaline probably acts on alpha 2-adrenoceptors in the central nervous system to produce sympathoinhibition.

Animals↗
PubMed1991

Noradrenaline-ATP corelease and cotransmission following activation of nicotine receptors at postganglionic sympathetic axons.

In rabbit mesenteric arteries, nicotine-evoked vasoconstrictor responses were markedly reduced by prazosin, slightly reduced after desensitization by alpha, beta-methylene ATP, and abolished by combined treatment with prazosin and alpha, beta-methylene ATP. In guinea-pig vasa deferentia preincubated with [3H]noradrenaline, nicotine elicited contractions as well as an overflow of tritium and of ATP. The contractions were greatly reduced by prazosin and abolished after additional desensitization by alpha, beta-methylene ATP. The nicotine-induced overflow of tritium was not changed by either treatment. The overflow of ATP was decreased by prazosin but not diminished further after additional desensitization by alpha, beta-methylene ATP. Activation of prejunctional nicotine receptors elicits a corelease of noradrenaline and ATP which leads to cotransmission in both tissues.

Adenosine Triphosphate↗
PubMed1991

Adrenergic and purinergic cotransmission in nicotine-evoked vasoconstriction in rabbit ileocolic arteries.

The possible involvement of ATP, in addition to noradrenaline, in nicotine-evoked vasoconstriction was studied in branches of the ileocolic artery of the rabbit. For measurement of vasoconstrictor responses, the arteries were simultaneously incubated and perfused. For measurement of the release of [3H]-noradrenaline, they were preincubated with [3H]-noradrenaline and then superfused. Prazosin (0.1 mumol/l) antagonized the constrictor effect of exogenous noradrenaline but not that of exogenous ATP. Desensitization of P2X-receptors by alpha, beta-methylene ATP markedly attenuated the effect of exogenous ATP but not that of noradrenaline. The presumed P2-purinoceptor antagonist suramin (100 mumol/l) reduced the maximal contraction obtainable with noradrenaline and shifted the concentration-response curve for the constrictor effect of alpha, beta-methylene ATP to the right, but did not change the effect of ATP. Nicotine elicited monophasic vasoconstrictions which faded while nicotine was still in the medium. The concentration-response curve was bell-shaped with an EC50 of 50 mumol/l and a maximal effect at 180 mumol/l, and the exposure time-response curve indicated that responses were maximal after 5 s of contact of nicotine (180 mumol/l) with the tissue. Neither prazosin 0.1 mumol/l nor desensitization by alpha,beta-methylene ATP changed the time course of the response to nicotine, but both depressed the magnitude of the responses over the whole concentration- and exposure time-response curves. The depression was greater with prazosin than with alpha,beta-methylene ATP. Desensitization by alpha,beta-methylene ATP or addition of suramin 100 mumol/l practically abolished the prazosin-resistant part of the response. The effect of nicotine was blocked by hexamethonium as well as by sympathetic denervation by 6-hydroxydopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Release of noradrenaline and ATP by electrical stimulation and nicotine in guinea-pig vas deferens.

Effects of electrical stimulation and nicotine on ATP and tritium outflow and smooth muscle tension were studied in the guinea-pig isolated vas deferens preincubated with [3H]-noradrenaline. ATP was measured using the luciferase technique. Electrical stimulation caused biphasic contractions and an acceleration of ATP and tritium outflow. The contraction amplitude and the overflow of ATP increased markedly, whereas the overflow of tritium increased only slightly with the frequency of stimulation (1-10 Hz; constant number of 60 pulses). The contraction amplitude did not increase with an increase in pulse number (20-540 pulses; constant frequency of 5 Hz), whereas the overflow of ATP increased slightly, and that of tritium markedly. Nicotine caused monophasic, transient contractions and, again, an acceleration of ATP and tritium outflow. Contractions, ATP and tritium overflow increased with the concentration of nicotine (56-320 mumol/l) in an approximately parallel manner. The influence of some drugs on responses to electrical stimulation (60 pulses, 5 Hz) and nicotine (180 mumol/l) was investigated. Tetrodotoxin blocked all effects of electrical stimulation but did not change those of nicotine. The reverse was true for hexamethonium. Neither electrical stimulation nor nicotine caused contraction or an increase in ATP outflow after pretreatment with 6-hydroxydopamine. The main effects of prazosin 0.3 mumol/l were to reduce electrically evoked contractions (above all second phase) as well as nicotine-evoked contractions and the nicotine-evoked overflow of ATP (the latter by about 81%). Prazosin also tended to diminish the electrically evoked overflow of ATP. alpha,beta-Methylene-ATP 10 mumol/l elicited a transient contraction and ATP overflow on its own. The main change in the subsequent state of desensitization was a decrease of the first phase of electrically evoked contractions. The main effects of prazosin combined with desensitization by alpha,beta-methylene-ATP were marked decreases of electrically evoked contractions (by 94%), the electrically evoked overflow ATP (by 66%), nicotine-evoked contractions (by 97%) and the nicotine-evoked overflow of ATP (by 70%). It is concluded that both electrical stimulation and nicotine release noradrenaline and ATP in guinea-pig vas deferens. Only part of the evoked overflow of ATP (about 32%) is neural in origin. Another part probably originates from smooth muscle cells where it is released by neurogenic noradrenaline acting at alpha 1-adrenoceptors. Corelease leads to cotransmission: electrically as well as nicotine-evoked contractions consist of adrenergic and purinergic components. Varying types of stimulation release cotransmitter mixtures of varying composition.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1991

"Real time" measurement of endogenous dopamine release during short trains of pulses in slices of rat neostriatum and nucleus accumbens: role of autoinhibition.

Release of endogenous dopamine elicited in slices of rat neostriatum or nucleus accumbens by a single electric pulse or by trains of 4 or 10 pulses was examined using fast cyclic voltammetry. Single electric pulses gave rise to a marked and transient increase in the extracellular concentration of dopamine in the neostriatum (by 0.43 mumol/l) and nucleus accumbens (by 0.39 mumol/l). The overflow elicited by subsequent pulses delivered at a frequency of 0.2 Hz caused separate but much smaller peaks of dopamine concentration, whereas the overflow elicited by subsequent pulses delivered at 1 Hz caused only a shoulder in the descending limb of the peak due to pulse 1. Four pulses at 5 Hz produced a monophasic response that was higher than the single pulse-evoked peak. Nomifensine 1 mumol/l greatly increased and prolonged the evoked overflow of dopamine. In the absence of nomifensine, metoclopramide 0.3 mumol/l did not change the response to a single pulse or 4 pulses delivered at 0.2 Hz but increased the response to 4 or 10 pulses at 1 Hz and to 4 pulses at 5 Hz. In the presence of nomifensine, metoclopramide increased the response to a single pulse as well as, to a greater extent, the response to 4 pulses at 0.2 Hz and 4 pulses at 1 Hz. Sulpiride 1 mumol/l produced effects similar to those of metoclopramide in the neostriatum in the presence of nomifensine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Species differences in presynaptic serotonin autoreceptors: mainly 5-HT1B but possibly in addition 5-HT1D in the rat, 5-HT1D in the rabbit and guinea-pig brain cortex.

The pharmacological properties of presynaptic serotonin autoreceptors were compared in slices of rat, rabbit, and guinea-pig brain cortex. The slices were preincubated with 3H-serotonin and then superfused with medium containing fluvoxamine 3 mumol/l and stimulated four times by trains of four pulses delivered at 100 Hz. Cumulative concentration-response curves were determined and used for the calculation of agonist EC50 values and maximal effects and antagonist KB values. Unlabelled serotonin itself and the serotonin receptor agonists 5-carboxamidotryptamine (5-CT), 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969) and (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) reduced the stimulation-evoked overflow of tritium with a rank order of potency 5-CT = RU 24969 greater than serotonin greater than 8-OH-DPAT in the rat and 5-CT greater than serotonin greater than RU 24969 greater than 8-OH-DPAT in the rabbit and guinea-pig. Ipsapirone caused no change. Metitepine and metergoline antagonized the effect of 5-CT; the KB values were lower in the rabbit and guinea-pig than in the rat. Yohimbine at up to 1 mumol/l did not reduce the evoked overflow of tritium and did not antagonize the inhibitory effect of 5-CT in the rat but reduced the evoked overflow in the rabbit and counteracted the effect of 5-CT in the guinea-pig. (-)-Propranolol, conversely, reduced the evoked overflow of tritium in the rat but neither reduced the evoked overflow nor antagonized the effect of 5-CT in the rabbit and guinea-pig. Isamoltane did not significantly change the effect of 5-CT in any species. In the rat, it also failed to antagonize the inhibitory effect of 8-OH-DPAT but did antagonize the effect of RU 24969. The inhibition caused by 8-OH-DPAT persisted in the presence of idazoxan but was attenuated by metitepine in all species. The experimental conditions used permit the determination of the constants of agonist and antagonist action undistorted by autoinhibition. The results confirm the view that the serotonin axons of rat brain possess 5-HT1B autoreceptors. They show by direct comparison under identical conditions that the autoreceptors in rabbit and guinea-pig are very similar to each other but differ markedly from those in the rat. The results give additional credence to previous suggestions that, in the rabbit and guinea-pig, the autoreceptors are 5-HT1D. The serotonin axons of rat brain cortex may possess 5-HT1D in addition to 5-HT1B autoreceptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Contraction-mediating alpha 2-adrenoceptors in the mouse vas deferens.

The question of the existence of postjunctional, contraction-mediating alpha 2-adrenoceptors, in addition to the known alpha 1-adrenoceptors, was studied in the mouse isolated vas deferens. Both the alpha 1-selective agonist phenylephrine and the alpha 2-selective agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) caused contraction of the vas deferens. In the presence of the alpha 1-selective antagonist prazosin (added in order to prevent an alpha 1 component in the effect of high concentrations of UK 14,304), the alpha 2-selective antagonist yohimbine and idazoxan shifted the concentration-response curve of UK 14,304 to the right in a manner compatible with competitive antagonism and with dissociation constants KB indicating the involvement of alpha 2-adrenoceptors. The maximal contraction elicited by UK 14,304 (in the presence of prazosin) was much lower than the maximal contraction elicited by phenylephrine. The effect of UK 14,304 was not changed by the P2-purinoceptor agonist alpha,beta-methylene-ATP and was reduced by neuropeptide Y, but was markedly enhanced by relatively low concentrations of phenylephrine. When the sympathetic fibres of the vas deferens were stimulated by trains of ten widely spaced (0.5 Hz) electric pulses, the tissue responded with ten separate twitches in which purinergic and adrenergic components were isolated by prazosin and suramin, respectively. Prazosin reduced the first adrenergic twitch in these trains at concentrations close to its KB value at alpha 1-adrenoceptors, whereas yohimbine and idazoxan reduced the first adrenergic twitch at concentrations far lower than their KB values at alpha 1-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1991

Subclassification of the presynaptic alpha 2-autoreceptors in rabbit brain cortex.

1. alpha 2-Adrenoceptor binding sites have been subclassified into alpha 2A sites of which a main characteristic is very low affinity for prazosin, and alpha 2B sites with relatively high affinity for prazosin. The presynaptic alpha 2-autoreceptors in rabbit brain cortex were studied in order to classify them in terms of alpha 2A and alpha 2B. Release of [3H]-noradrenaline in cortical slices was elicited by trains of 4 pulses delivered at 100 Hz. 2. Clonidine caused concentration-dependent inhibition of the stimulation-evoked overflow of tritium, with an EC50 of 7.5 nM and a maximal inhibition by 96%. 3. The following alpha-adrenoceptor antagonists shifted the concentration-response curve of clonidine to the right (antagonist-receptor dissociation constants KD in brackets): yohimbine (14 nM), 2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidazo le (BRL 44408; 15 nM) and 1,2-dimethyl-2,3,9,13betetrahydro-1H-dibenzo[c,f]imidazo[1,5-a]aze pine (BRL 41992; 630 nM). Prazosin 1 microM and 2-[2-[4-(o-methoxyphenyl)piperazine-1-yl]-ethyl]-4,4-dimethyl-1,3 (2H,4H)-isoquinolinedione (AR-C 239) 1 microM failed to antagonize the effect of clonidine. Higher concentrations of prazosin and AR-C 239 greatly accelerated the basal efflux of tritium. 4. The method used permits the functional determination of antagonist affinities undistorted by endogenous alpha 2-autoinhibition. A comparison with affinities derived from radioligand binding experiments indicates that the presynaptic alpha 2-autoreceptors in rabbit brain cortex are markedly different from the alpha 2B-subtype and probably belong to the prazosin-insensitive alpha 2A-subtype.

Adrenergic alpha-Antagonists↗
PubMed1991

Nucleotides as cotransmitters in vascular sympathetic neuroeffector transmission.

Postganglionic sympathetic cotransmission by noradrenaline (NA) and adenosine 5'-triphosphate (ATP) was studied in isolated arteries from rabbits using as tools alpha-adrenoceptor antagonists and alpha, beta-methylene-ATP which first activates and then desensitizes purine P2X receptors. In the pulmonary artery, NA was the only chemical signal responsible for neurogenic vasoconstriction. In sharp contrast, ATP was the only signal eliciting electric as well as mechanical postjunctional responses in small jejunal arteries. Mixed adrenergic and purinergic transmission was found in the largest ramus caecalis of the ileocolic artery. The purinergic component prevailed in short pulse trains and early in long trains, whereas the adrenergic component prevailed in the late phases of long (20 s) trains. Prejunctional alpha 2-adrenergic autoinhibition markedly depressed purinergic as well as adrenergic transmission as soon as a latency of about 2 s was exceeded.

Adenosine Triphosphate↗