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A H Mulder

Publications and source records attributed to A H Mulder.

At least 127 records · Page 7Linked to original sources
PubMed1991

The electrically stimulated release of [3H]noradrenaline from nucleus tractus solitarii slices in vitro is modulated via mu-opioid receptors.

The electrically stimulated release of [3H]noradrenaline ([3H]NA) from slices of the nucleus tractus solitarii (NTS) from the rat in vitro was inhibited by the alpha 2-adrenoceptor agonist, clonidine, in a concentration-dependent manner and enhanced by the alpha 2-adrenoceptor antagonist, yohimbine. Phenylephrine, isoprenaline, carbachol, quinpirole and SKF 38393, all at 10(-6) M, did not affect the stimulus-evoked release of [3H]NA. The opioid peptides, alpha- and gamma-endorphin, did not have a significant effect on the stimulus-evoked release of [3H]NA; however, beta-endorphin reduced it in a concentration-dependent manner. [Leu5]Enkephalin also reduced [3H]NA release, but higher concentrations were necessary. The selective delta opioid receptor agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6 (DSTBULET), as well as the selective kappa opioid receptor agonist, U-69593, were not effective. The selective mu opioid receptor agonist, [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO), concentration dependently reduced the stimulus-evoked release of [3H]NA to the same extent as beta-endorphin did. Naloxone, while having no effect on stimulus-evoked [3H]NA release, antagonized the effect of DAGO. These results corroborate that the release of NA from noradrenergic terminals in the NTS region of the medulla oblongata of the rat is modulated via alpha 2-adrenoceptors and suggest that the release of NA in the NTS in rats is also modulated via mu opioid receptors.

Adrenergic alpha-Agonists↗
PubMed1991

Pharmacological profile of various kappa-agonists at kappa-, mu- and delta-opioid receptors mediating presynaptic inhibition of neurotransmitter release in the rat brain.

1. The potency, relative efficacy and selectivity of a series of kappa-opioid receptor agonists at the mu-, delta- and kappa-opioid receptors mediating inhibition of electrically-induced (radiolabelled) neurotransmitter release from superfused rat brain slices was determined. 2. With regard to their potencies at kappa-receptors mediating inhibition of striatal [3H]-dopamine release, the highest pD2 value (8.7) was found for bremazocine and the lowest (7.1) for U50488; the pD2 values for ethylketocyclazocine (EKC), tifluadom, U69593 and PD117302 were between 8.0 and 8.3. There were no marked differences between the relative efficacies of the kappa-agonists (maximum inhibition being 60-70%). In contrast to the other kappa-agonists, at a concentration of 1 microM, PD117302 caused a significant (25-40%) increase of the spontaneous efflux of tritium. 3. None of the kappa-agonists significantly affected striatal [14C]-acetylcholine (ACh) release, with the exception of a slight inhibitory effect of EKC. The delta-receptor-mediated inhibitory effect of [D-Ala2, D-Leu5]enkephalin (DADLE) on [14C]-ACh release was antagonized in a concentration-dependent manner by bremazocine (0.1 and 1.0 microM) and also partially by EKC (1 microM), but not by the other kappa-agonists. The pA2 value for bremazocine as an antagonist at the delta-receptors involved was 8.0, compared to 7.6 for naloxone. 4. None of the kappa-agonists significantly affected cortical [3H]-noradrenaline (NA) release, with the notable exception of tifluadom, which strongly inhibited release by activating mu-receptors. The mu-receptor-mediated inhibitory effect of Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAMGO) on [3H]-NA release was antagonized in a concentration-dependent manner by bremazocine and EKC, but not by the other K-agonists. The pA2 value for bremazocine as an antagonist at the mu-receptors involved was 8.2, compared to 8.6 for naloxone. 5. Thus, whereas U69593 and PD1 17302 display high potency and selectivity towards K-opioid receptors, the potent benzomorphan K-agonists bremazocine and EKC also appear to be strong mu-opioid receptor antagonists.

Acetylcholine↗
PubMed1991

Opioid-receptor-mediated inhibition of [3H]dopamine but not [3H]noradrenaline release from rat mediobasal hypothalamus slices.

The modulation of the electrically evoked release of [3H]dopamine (DA) and [3H]noradrenaline (NA) by opioid receptor activation was examined in superfused slices of rat mediobasal hypothalamus (MBH). [3H]DA release was inhibited (maximally by 30-35%) by both the selective kappa-agonist U 50,488 (1 nM to 1 microM) and the selective mu-agonist DAGO (0.01-1 microM) but not by the delta-selective agonist DPDPE (1 microM). Naloxone partly antagonized the inhibitory effect of U 50,488 and completely that of DAGO, whereas the selective kappa-antagonist norbinaltorphimine (nor-BNI) only antagonized the inhibition caused by U 50,488. The dopamine D2 receptor agonist quinpirole as well as the alpha 2-adrenoceptor agonist oxymetazoline both decreased (by 25-30%) the evoked overflow of [3H]DA. The evoked release of [3H]NA was not modulated by any of the opioid agonists nor by quinpirole. However, the alpha 2-adrenoceptor agonist oxymetazoline inhibited the release of [3H]NA by 30-40%. Activation of alpha 2-adrenoceptors by oxymetazoline prevented the inhibitory effect of U 50,488, but not DAGO, on evoked [3H]DA release, whereas the selective kappa-antagonist nor-BNI antagonized the inhibition by oxymetazoline of [3H]DA, but not [3H]NA, release. In conclusion, activation of both kappa- and mu-opioid receptors results in an inhibition of evoked DA release from MBH slices but does not modulate NA release. Therefore, several of the reported effects of opioids on hormone secretion may be an (indirect) consequence of a reduction of DA release.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

Opioid receptor-mediated inhibition of dopamine and acetylcholine release from slices of rat nucleus accumbens, olfactory tubercle and frontal cortex.

The modulation of the electrically evoked release of [3H]dopamine (DA) and [14C]acetylcholine (ACh) by opioid receptor activation was examined in superfused slices from rat nucleus accumbens, olfactory tubercle, and frontal cortex. In all brain areas examined, [3H]DA release was inhibited by the kappa agonist, U 50,488 (1-100 nM), and this inhibition was fully antagonized by the selective kappa antagonist, norbinaltorphimine (nor-BNI). In the frontal cortex, the mu agonist, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, 0.01-1 microM), also inhibited the evoked release of tritium. However, further experiments (including the use of the D2-receptor agonist, LY 171555, and the alpha 2-adrenoceptor agonist, oxymetazoline) suggest strongly that in the frontal cortex DAGO only inhibits the release of [3H]catecholamine from noradrenergic nerve terminals, despite the use of desimipramine to prevent the uptake of [3H]DA into these terminals. [14C]ACh release from both the nucleus accumbens and olfactory tubercle, but not from the frontal cortex, was inhibited by DAGO (0.01-1 microM) and the delta agonist, [D-Pen2,D-Pen5]enkephalin (DPDPE, 0.01-1 microM). These inhibitory effects were antagonized by 0.1 microM naloxone but not by 3 nM nor-BNI. The irreversible delta ligand, fentanyl isothiocyanate (FIT, 1 microM), only antagonized the inhibition caused by DPDPE. The results indicate that the inhibitory effects of opioids on the in vitro release of DA from dopaminergic nerve fibres arising from the substantia nigra and the ventral tegmental area are mediated by presynaptic kappa receptors only. In those regions where ACh release is modulated by opioids, the type of opioid receptor involved may depend on the type of neuron, i.e. interneuron or afferent neuron.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

Ontogeny of mu-, delta- and kappa-opioid receptors mediating inhibition of neurotransmitter release and adenylate cyclase activity in rat brain.

The ontogeny was examined of functional opioid receptors mediating presynaptic inhibition of neurotransmitter release and inhibition of dopamine (DA)-sensitive adenylate cyclase in the rat brain, using highly selective agonists for mu-, delta- and kappa-receptors. On gestational day 17 (E17) strong inhibitory effects of the selective mu-agonist DAGO on the electrically evoked release of [3H]noradrenaline from cortical slices and of the selective kappa-agonist U-50,488 on the electrically evoked release of [3H]DA from striatal slices were found. Electrically evoked release of [3H]acetylcholine from striatal slices was not detectable before postnatal day 7 (P7), but on that day it was already strongly inhibited by the selective delta-agonist DPDPE. Although mu- and delta-opioid receptors coupled to DA-sensitive adenylate cyclase in the striatum are likely to be physically associated in an opioid receptor complex in the adult, they were found to develop asynchronously. Whereas selective activation of mu-receptors with DAGO resulted in an inhibition of D1 dopamine receptor-stimulated adenylate cyclase activity on E17, activation of delta-receptors with DPDPE was not effective until P14. This study confirms the early appearance of mu- and kappa-opioid receptors and the relatively late development of delta-opioid receptors in the rat brain. Most importantly, it shows that in an early stage of development opioids are already able to mediate modulation of noradrenergic (via activation of mu-receptors) and dopaminergic (via activation of mu- and kappa-receptors) neurotransmission processes. Therefore, these opioid receptor types could play a role in brain development and/or developmental disturbances.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

Mu-opioid receptors mediate the inhibitory effect of opioids on dopamine-sensitive adenylate cyclase in primary cultures of rat neostriatal neurons.

The receptors mediating the inhibition of D1 dopamine receptor-stimulated adenylate cyclase by opioids were examined in primary cultures of rat neostriatal neurons. Adenylate cyclase activity was dose-dependently increased by the selective D1 dopamine receptor agonist SKF 38393 (EC50 = 0.05 microM). This stimulation was fully antagonized by the selective D1 dopamine receptor antagonist SCH 23390 (1 microM). SKF 38393 (1 microM)-stimulated adenylate cyclase activity was strongly reduced (by almost 60%) by the highly selective mu-agonist [D-Ala2, MePhe4, Gly-ol5]-enkephalin (DAGO; EC50 = 0.006 microM) and high concentrations of the selective delta-agonist [D-Ser2(O-tert-butyl), Leu5]-enkephalyl-Thr6 (DSTBU-LET; EC50 = 0.13 microM) but not by the selective delta-agonist [D-penicillamine2, D-penicillamine5]enkephalin (DPDPE). D1 dopamine receptor-stimulated adenylate cyclase activity was also slightly reduced (by approximately 20%) by high concentrations of the kappa-agonist U50,488 (EC50 = 0.63 microM). The inhibitory effects of submaximally effective concentrations of DAGO, DSTBULET, and U50,488 were equally well antagonized by the mu-opioid receptor-selective antagonist naloxone (EC50 of approximately 0.1 microM). Neither the irreversible delta-ligand fentanyl isothiocyanate (1 microM) nor the reversible delta-antagonist ICI 174864 (1 microM) reversed the inhibitory effects of DSTBULET. The inhibitory effects of DAGO and U50,488 were equally well reversed by high concentrations (greater than 0.1 microM) of the kappa-opioid receptor-selective antagonist norbinaltorphimine. The effect of DAGO (1 microM) was already detectable after 1 day in culture, whereas DPDPE (1 microM) had no effect even after 28 days in culture. These data indicate that an homogeneous population of mu-opioid receptors coupled as inhibitors to D1 dopamine receptor-stimulated adenylate cyclase is expressed in rat neostriatal neurons in primary culture.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Selective effects of [D-Ser2(O-t-butyl),Leu5]enkephalyl-Thr6 and [D-Ser2(O-t-butyl),Leu5]enkephalyl-Thr6 (O-t-butyl), two new enkephalin analogues, on neurotransmitter release and adenylate cyclase in rat brain slices.

The selectivity and potency of two new enkephalin-derived delta-opioid receptor agonists, DSTBULET ([D-Ser2(O-t-butyl),Leu5]enkephalyl-Thr6) and BUBU ([D-Ser2(O-t-butyl),Leu5]enkephalyl-Thr6(O-t-butyl] were determined with functional tests in vitro of mu-, delta- and kappa-opioid receptor activation in the rat brain. Both peptides concentration dependently (1 nM-1 microM) inhibited the release of radiolabeled acetylcholine (ACh) from striatal slices (pD2 7.6-7.9), an effect exclusively mediated by delta-opioid receptor activation. Fentanyl isothiocyanate (FIT), an irreversible delta-antagonist, completely blocked the inhibitory effects of DSTBULET and BUBU. Up to a concentration of 1 microM, the peptides did not affect striatal [3H]dopamine (DA) release nor cortical [3H]noradrenaline (NA) release, processes which are known to be inhibited by opioids activating kappa and mu-receptors, respectively. Furthermore, both DSTBULET and BUBU caused a strong inhibition (pD2 8.2-8.3) of D-1 dopamine receptor-stimulated cyclic AMP efflux from striatal slices, an effect known to be mediated by mu- and/or delta-opioid receptor activation. However, the peptides were without effect when D-1 and D-2 dopamine receptors were stimulated simultaneously, a situation in which only mu-agonists are able to inhibit the resulting cAMP efflux. In conclusion, DSTBULET and BUBU appear to display a high selectivity and potency toward functional delta-opioid receptors in the brain.

Adenylyl Cyclases↗
PubMed1989

Establishment and characterization of long-term primary mouse urothelial cell cultures.

Long-term mouse urothelial cell cultures were routinely established from explants of neonatal mouse bladders. Foci of proliferating cells could be observed one week after the initiation of the explant cultures. These persisted throughout the culture period and up to one year. Expression of keratin proteins confirmed the epithelial nature of the cultured cells. Morphologic analysis of nuclei sorted after DNA flow cytometry revealed a population of DNA-tetraploid and octoploid cells with large nuclei and prominent nucleoli in addition to a DNA-diploid cell population. Both cell populations showed DNA replicative activity as reflected by bromodeoxyuridine incorporation studies and mitotic activity. These long-term primary mouse urothelial cell cultures may prove useful for studies on urothelial cell kinetics and bladder carcinogenesis.

Animals↗
PubMed1989

Mu- and delta-opioid receptor-mediated inhibition of adenylate cyclase activity stimulated by released endogenous dopamine in rat neostriatal slices; demonstration of potent delta-agonist activity of bremazocine.

Rat neostriatal slices were superfused with medium containing 0.1 to 30 microM of the dopamine (DA)-releasing agent D-(+)-am-phetamine (AMPH) and the D-2 DA receptor antagonist (-)-sulpiride (10 microM) in the absence or presence of mu-, delta-, and kappa-selective opioids. AMPH dose-dependently enhanced the cyclic AMP production, as measured by its efflux from striatal slices, whereas simultaneous blockade of D-2 DA receptors by (-)-sulpiride strongly potentiated this effect. Both the mu-opioid receptor selective agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (0.01-3 microM) and the delta-opioid receptor selective agonist [D-Phe2-D-Pen5]enkephalin (DPDPE, 0.01-3 microM) inhibited the cyclic AMP efflux, stimulated by 10 microM AMPH in the presence of (-)-sulpiride, by 70 to 80%. The highly selective kappa-opioid receptor agonist U 50,488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrol-idinyl)- cyclohexyl]benzeneacetamide methanesulfonate hydrate) (0.01-1 microM) had no effect. In contrast, the purported kappa-opioid receptor agonist bremazocine (3-300 nM) inhibited the stimulated adenylate cyclase activity to a similar extent as did [D-Ala2-MePhe4,Gly-ol5]enkephalin and DPDPE. Moreover, the selective irreversible delta-antagonist fentanyl isothiocyanate reversed both the inhibition caused by DPDPE and that caused by bremazocine, whereas the kappa-selective antagonist norbinaltorphimine showed no differences in its potency to antagonize the inhibitory effects of the different opioid agonists. The results indicate that opioids, by activating mu- or delta-, but not kappa-opioid receptors may cause a profound inhibition of adenylate cyclase activity stimulated by activation of (postsynaptic) D-1 DA receptors upon the (presynaptic) release of DA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1988

Antagonist activity of the cyclic somatostatin analogue CTP at mu- but not delta- and kappa-opioid receptors involved in presynaptic inhibition of neurotransmitter release.

In the present study the opioid receptor antagonist properties of the conformationally constrained cyclic octapeptide D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (CTP), which is derived from somatostatin, were investigated, using in vitro functional paradigms of central mu-, delta- and kappa-opioid receptors. Activation of mu-opioid receptors by the enkephalin analogues DADLE or DAGO resulted in a strong inhibition (by 60-70%) of the (electrically evoked) release of [3H]noradrenaline (NA) from superfused cortical slices. This inhibitory effect was antagonized by CTP in a competitive fashion (pA2 value 7.7-7.9). Activation of kappa-opioid receptors by bremazocine selectively inhibited (by 45-50%) the release of [3H]dopamine (DA) from striatal slices, whereas activation of delta-opioid receptors by DADLE caused an inhibition (by 55-60%) of striatal [14C]acetylcholine (ACh) release, but neither of these inhibitory effects was affected by CTP. By itself, CTP inhibited cortical [3H]NA release (by 35-40%), but it did not affect the release of [3H]DA nor that of [14C]ACh from striatal slices. The inhibitory effect of CTP was not antagonized by naloxone. The data indicate that CTP selectively antagonizes mu-opioid receptors, involved in presynaptic inhibition of NA release in the brain. In addition, the peptide by itself causes an inhibition of NA release via a non-opioid receptor-mediated process.

Adrenergic alpha-Agonists↗
PubMed1988

Mu-, delta- and kappa-opioid receptor-mediated inhibition of neurotransmitter release and adenylate cyclase activity in rat brain slices: studies with fentanyl isothiocyanate.

We investigated the effects of [D-Ala2,D-Leu5]enkephalin (DADLE). [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO), [D-Pen2,D-Pen5]enkephalin (DPDPE) (0.01-1 microM) and bremazocine (0.001-0.3 microM) on the electrically evoked release of radiolabelled neurotransmitters and on the dopamine (DA)-stimulated cyclic AMP efflux from superfused rat brain slices. The differential inhibitory effects of these agonists on the evoked neurotransmitter release indicate that the opioid receptors mediating presynaptic inhibition of [3H]noradrenaline (NA, cortex), [14C]acetylcholine (ACh, striatum) and [3H]DA (striatum) release represent mu, delta and kappa receptors, respectively. In agreement with this classification, preincubation (60 min) of the slices with the delta-opioid receptor-selective irreversible ligand, fentanyl isothiocyanate (FIT, 0.01-1 microM), antagonized the inhibitory effects of DADLE and DPDPE on striatal [14C]ACh release only. On the other hand, the D-1 DA receptor-stimulated cyclic AMP efflux from striatal slices appeared to be inhibited by activation of mu as well as of delta receptors. In this case, the reversible mu antagonist, naloxone (0.1 microM), fully antagonized the inhibitory effect of the mu agonist, DAGO, without changing the effect of the delta agonist DPDPE but was ineffective as an antagonist in slices pretreated with FIT (1 microM). The inhibitory effect of DAGO on the electrically evoked [3H]NA release was antagonized by naloxone whether the receptors were irreversibly blocked by FIT or not. These data not only further support the existence of independent presynaptic mu-, delta- and kappa-opioid receptors in rat brain but also evidence strongly that mu and delta receptors mediating the inhibition of DA-sensitive adenylate cyclase could share a common binding site (for naloxone and FIT) and, therefore, may represent constituents of a functional opioid receptor complex.

Acetylcholine↗
PubMed1988

Interferon expression in the testes of transgenic mice leads to sterility.

A plasmid containing the mouse interferon-alpha 1 gene under control of the mouse metallothionein-I promoter was used for the construction of transgenic mice. Four transgenic mice (two males and two females) were obtained containing 1 to over 10 copies of the introduced DNA. Both males appeared to be sterile. One of the female mice founded a transgenic strain in which the foreign DNA was transmitted to her offspring in a Mendelian fashion. In this strain most male animals are sterile or turn sterile with time. Northern blot analysis of several tissues of these animals shows that expression of the introduced interferon gene occurs only in the testis. In some of the animals biologically active interferon could also be detected in testes homogenates. Histological examination of testis tissue shows an ongoing degeneration of spermatogenic cells leading to calcium deposits and complete atrophy of the seminiferous tubules.

Animals↗
PubMed1988

Use of syngeneic monoclonal antibodies in the therapy of disseminated myeloid leukemic cells.

A syngeneic monoclonal antibody (MAb) (IC5F5) was successfully used in the immunotherapy of Rauscher-virus-induced myeloid leukemic RMB-I cells. It is directed to a virus-encoded, but aberrantly processed protein, which is expressed on the cell membrane. When applied in vivo, it binds only to RMB-I tumor cells. BALB/c mice were inoculated i.p. or i.v. with 10(7) RMB-I cells and died within 2-3 weeks due to increasing tumor load. Mice inoculated i.p. were completely cured by daily injections of ascites containing IC5F5. Disseminated tumor cells in liver and hemopoietic organs were observed after i.v. inoculation. Daily treatment with MAbs resulted in survival beyond 90 days. No antigenic modulation was observed when tumor tissue was analyzed 2-10 days after treatment. Treatment was successful even when therapy was postponed until day 5 following inoculation of tumor cells. When the number of ascites injections was reduced, survival was identical to that observed among repeatedly treated mice. Ten- and 100-fold dilution of ascites fluid diminished the number of survivors, but still resulted in a median survival time of 38 and 20 days, respectively, as compared to 14 days for untreated mice.

Animals↗
PubMed1988

Fentanyl isothiocyanate reveals the existence of physically associated mu- and delta-opioid receptors mediating inhibition of adenylate cyclase in rat neostriatum.

Dopamine D-1 receptor-stimulated cyclic AMP efflux from superfused rat neostriatal slices was strongly inhibited by the delta-opioid receptor agonist, [D-Pen2, D-Pen5]enkephalin (DPDPE, 1 microM), and by the mu-opioid receptor agonist, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, 1 microM). Naloxone (0.1 microM) fully antagonized the inhibitory effect of DAGO, leaving that of DPDPE virtually unchanged. Preincubation of the slices with the irreversible delta receptor ligand, fentanyl isothiocyanate (FIT, 1 microM) did not affect the inhibitory effect of DAGO, but prevented that of DPDPE. Naloxone no longer antagonized the inhibitory effect of DAGO when the delta receptors were selectively and irreversibly blocked by FIT. These data indicate that FIT and naloxone, acting on delta and mu receptors, respectively, may share a common binding site, suggesting the involvement of a functional mu, delta-opioid receptor-complex.

Adenylyl Cyclase Inhibitors↗
PubMed1988

Alpha 2-adrenoceptor mediated inhibition of the release of radiolabelled 5-hydroxytryptamine and noradrenaline from slices of the dorsal region of the rat brain.

Possible local interactions between noradrenergic and serotonergic systems in the dorsal raphe region of the rat were investigated by studying the effects of various drugs on depolarization (20 mmol/l K+)-induced release of [3H]5-hydroxytryptamine (5-HT) and [3H]noradrenaline (NA) in vitro using a superfusion method. Exogenous 5-HT did not influence the release of [3H]NA. However, NA (in the presence of 10 mumol/l desipramine) as well as the selective alpha 2-adrenoceptor agonists clonidine and oxymetazoline strongly inhibited [3H]5-HT release. The selective alpha 1-adrenoceptor agonists phenylephrine and methoxamine did not affect the release of either [3H]5-HT or [5H]NA. The inhibition by NA of both [3H]5-HT and [3H]NA release was not affected by the beta-adrenoceptor antagonist sotalol nor by the selective alpha 1-adrenoceptor antagonist prazosin. However, phentolamine and the selective alpha 2-adrenoceptor antagonists yohimbine and rauwolscine competitively antagonized the inhibitory effect of NA on [3H]NA release (respective pA2-values 7.5 and 8.3) and on [3H]5-HT release (respective pA2-values 7.7 and 8.2). Moreover, the release of [3H]NA and also, but to a lesser extent, that of [3H]5-HT were increased by the antagonists. It is concluded that the release of both 5-HT and NA in the dorsal raphe region may be subject to presynaptic inhibition by NA via activation of alpha 2-adrenoceptors.

Animals↗