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R Quirion

Publications and source records attributed to R Quirion.

At least 253 records · Page 14Linked to original sources
PubMed1990

Autoradiographic distribution of brain neurokinin-1/substance P receptors using a highly selective ligand [3H]-[Sar9,Met(O2)11]-substance P.

The autoradiographic distribution of neurokinin (NK)-1 receptors was visualized in the rat brain using the highly selective ligand, [3H]-[Sar9,Met(O2)11]-substance P. This ligand apparently binds to a single class of high affinity (Kd = 1.4 +/- 0.5 nM), low capacity (Bmax = 160 +/- 3.0 fmol/mg protein) sites in rat brain membrane preparations. The ligand selectivity profile reveals that substance P (SP) and unlabeled [Sar9,Met(O2)11]-SP are potent competitors of [3H]-[Sar9,Met(O2)11]-SP binding while NK-2 and NK-3 analogues are virtually inactive demonstrating the selectivity of this radioligand for the NK-1 receptor class. Autoradiographic data show that [3H]-[Sar9,Met(O2)11]-SP binding sites are broadly but discretely distributed in rat brain, the highest densities of sites being located in the external plexiform layer of the olfactory bulb, striatum, olfactory tubercule, amygdala-hippocampal area, endopiriform and entorhinal cortices, superior colliculus, locus coeruleus and substantia gelatinosa of the spinal cord. This distribution is similar, but not identical, to that previously reported for NK-1 sites using less selective ligands such as [125I]Bolton-Hunter SP. For example, some difference in labelling patterns are observed in the hippocampal formation. This could be explained by the existence of NK-1 receptor subtypes, only one of them being recognized by [3H]-[Sar9,Met(O2)11]-SP or by the greater selectivity of this radioligand for NK-1 over NK-2 and NK-3 receptor classes.

Animals↗
PubMed1990

Chronic estradiol treatment alters central cholinergic function in the female rat: effect on choline acetyltransferase activity, acetylcholine content, and nicotinic autoreceptor function.

The purpose of the present study was to determine the effects of chronic (2-month) estradiol (E2) treatment on cholinergic function in the frontal cortex, hippocampus and hypothalamus of the female rat. Chronic E2 treatment selectively increased choline acetyltransferase (ChAT) activity in the frontal cortex and decreased ChAT activity in the hypothalamus: hippocampal ChAT activity was not significantly changed. The decrease of ChAT activity in the hypothalamus was paralleled by a significant reduction in the content and release (basal and evoked) of acetylcholine (ACh) in this structure. Neither the content nor the release of ACh was altered in the frontal cortex. In the hippocampus, there was a significant increase in spontaneous ACh release; however, hippocampal ACh content and evoked ACh release were not changed. Chronic E2 treatment also altered nicotinic binding sites in these same regions as determined by saturation analysis of [3H]methylcarbamylcholine (MCC) to membranes. There was a decrease in the affinity and an increase in the density of [3H]MCC binding sites in hippocampal membranes and an increase in the density of [3H]MCC binding sites was observed in hypothalamic membranes. These alterations were paralleled by changes in nicotinic autoreceptor function within these two structures. In the hippocampus, the increase in spontaneous ACh release induced by MCC in control animals was no longer apparent after chronic treatment with E2. In hypothalamus, higher concentrations of the nicotinic agonist were required to increase spontaneous ACh release in slices from E2-treated rats as compared to control rats. Taken together, these results suggest that chronic E2 treatment decreases presynaptic cholinergic function in the female rat hippocampus and hypothalamus.

Acetylcholine↗
PubMed1990

Post-training injection of the acetylcholine M2 receptor antagonist AF-DX 116 improves memory.

The present study examined the effect of systemic post-training administration of the acetylcholine muscarinic M2 receptor antagonist AF-DX 116 on the acquisition of two 8-arm radial maze tasks. On a win-stay visual discrimination task, a light cue signalled the location of food in 4 randomly selected maze arms, and rats were required to visit each of the 4 lit arms twice within a trial. Rats were given one trial per day and injected immediately post-training on day 5. AF-DX 116 (0.5 and 1.0 mg/kg) significantly improved win-stay acquisition relative to vehicle-injected controls. On a win-shift task, rats were allowed to visit 4 randomly selected maze arms, followed by a delay period. After the delay, rats were returned to the maze for a retention test in which only those 4 arms not visited prior to the delay contained food. On the test (i.e. drug) trial, rats were removed from the maze after the first 4 choices and injected with AF-DX 116 or vehicle. The retention test was given following an 18 h delay. AF-DX 116 (2.0 mg/kg) significantly improved retention relative to vehicle controls. When the injections were given 2 h post-training, no effect on retention was observed in either task. The results demonstrate that post-training injection of the selective M2 receptor antagonist AF-DX 116 improves memory in a time-dependent manner. The findings may have implications for the cholinergic pharmacotherapy of Alzheimer's disease.

Animals↗
PubMed1990

Distribution of 125I-neurotensin binding sites in human forebrain: comparison with the localization of acetylcholinesterase.

The distribution of 125I-neurotensin binding sites was compared with that of acetylcholinesterase reactivity in the human basal forebrain by using combined light microscopic radioautography/histochemistry. High 125I-neurotensin binding densities were observed in the bed nucleus of the stria terminalis, islands of Calleja, claustrum, olfactory tubercle, and central nucleus of the amygdala; lower levels were seen in the caudate, putamen, medial septum, diagonal band nucleus, and nucleus basalis of Meynert. Adjacent sections processed for cholinesterase histochemistry demonstrated a regional overlap between the distribution of labeled neurotensin binding sites and that of intense acetylcholinesterase staining in all of the above regions, except in the bed nucleus of the stria terminalis, claustrum, and central amygdaloid nucleus, where dense 125I-neurotensin labeling was detected over areas containing only weak to moderate cholinesterase staining. At higher magnification, 125I-neurotensin-labeled binding sites in the islands of Calleja, supraoptic nucleus of the hypothalamus, medial septum, diagonal band nucleus, and nucleus basalis of Meynert were selectively associated with neuronal perikarya found to be cholinesterase-positive in adjacent sections. Moderate 125I-neurotensin binding was also apparent over the cholinesterase-reactive neuropil of these latter three regions. These data suggest that neurotensin (NT) may directly influence the activity of magnocellular cholinergic neurons in the human basal forebrain, and may be involved in the physiopathology of dementing disorders such as Alzheimer's disease, in which these neurons have been shown to be affected.

Acetylcholinesterase↗
PubMed1990

Neuropeptide Y receptor binding sites in human brain. Possible alteration in Alzheimer's disease.

Neuropeptide Y (NPY) and peptide YY (PYY) receptor sites were studied in human brain using saturation binding experiments and receptor autoradiography. Additionally, the affinities and densities of [3H]NPY binding sites were compared in the temporal cortex, hippocampus and putamen of patients dying from Alzheimer's disease (AD) and aged matched controls. High densities of [3H]NPY binding sites were found in the putamen (192 +/- 32 fmol/mg protein), followed by the hippocampus (165 +/- 42 fmol/mg protein) and temporal cortex (118 +/- 19 fmol/mg protein). Receptor autoradiography revealed that these sites were especially concentrated in certain layers of the hippocampus, laminae I and IV-V of the temporal cortex and the amygdalo-hippocampal area. No significant changes in [3H]NPY binding affinities were seen between the AD and aged-matched groups (Kd ranges: 2.5-6.8 nM). However, significant decreases in [3H]NPY receptor densities (Bmax) were found in temporal cortex (-43%) and hippocampus (-49%) in AD brains. No significant change in [3H]NPY Bmax values was found in the putamen. It is therefore possible that decreases in [3H]NPY receptor densities may be associated to the degenerative process taking place in certain brain regions in AD, although further work will be necessary to confirm this hypothesis. Part of this work was presented at the 17th Annual Meeting of the Society for Neuroscience.

Aged↗
PubMed1990

Quantitative autoradiographic distribution of multiple neurokinin binding sites in rat spinal cord.

As a means of evaluating the role of neurokinins (NKs) in spinal function, the present study examines the quantitative autoradiographic distribution in the rat spinal cord of [125I]Bolton-Hunter-substance P, (2-[125I]iodohistidyl1)-neurokinin A and [125I]Bolton-Hunter-eledoisin as respective radioligands for NK-1, NK-2 and NK-3 receptors. These putative NK receptor sub-types are clearly differentially distributed at the various levels of the spinal cord. NK-1 sites represent the most abundant population of spinal NK receptors. They are most concentrated in the dorsal and ventromedial borders of the dorsal horn, the intermediolateral nucleus of the thoracic cord and the phrenic motor nucleus in the cervical ventral horn. NK-2 and NK-3 sites are also present in the spinal cord, although in much lower quantities than NK-1 sites. NK-2 sites are mostly found along the dorsal and ventromedial borders of the dorsal horn, in a narrow band connecting the two lateral horns of the thoracic cord, around the central canal of the lumbar and sacral segments and lamina IX of the cervical ventral horn. NK-3 sites are most dense in the dorsal border of the dorsal horn, with moderate amounts in the lateral horn of the thoracic cord and around the central canal of lumbar and sacral segments. The differential distribution of these 3 classes of NK sites in the spinal cord suggests that each NK receptor sub-type could mediate specific sensory, autonomic and/or motor functions at the spinal level.

Animals↗
PubMed1990

Visualization of neurokinin-3 receptor sites in rat brain using the highly selective ligand [3H]senktide.

The autoradiographic distribution of the neurokinin (NK)-3 receptor sub-type was visualized in the rat brain using [3H]senktide, a highly selective ligand, [3H]Senktide apparently binds to a single class of high affinity (Kd = 2.8 +/- 1.0 nM), low capacity (Bmax = 31.2 +/- 3.0 fmol/mg protein) sites in rat brain cortex. The ligand selectivity pattern reveals that eledoisin and senktide are potent competitors of both [3H]senktide and [125I]Bolton-Hunter eledoisin binding sites demonstrating the NK-3 nature of these sites. Autoradiographic data show that [3H]senktide binding sites are concentrated in mid-cortical layers, supraoptic nucleus, zona incerta, basolateral nucleus of the amygdala and interpeduncular nucleus. Much lower densities of binding are seen in most other areas such as the caudate-putamen and cerebellum. This distribution is similar, but not identical, to that previously reported for NK-3 sites using less selective ligands. It is most likely because less selective probes also bind to other classes of NK receptors. The higher selectivity of [3H]senktide is thus an important advantage for the precise characterization of NK-3 receptor binding parameters.

Animals↗
PubMed1990

Subtypes of excitatory amino acid receptors involved in the stimulation of [3H]dopamine release from cell cultures of rat ventral mesencephalon.

N-methyl-D-aspartic acid (NMDA), quisqualic acid (QUIS), and kainic acid (KAIN), respective agonists for three excitatory amino acid (EAA) receptor subtypes, stimulated [3H]dopamine ([3H]DA) release from dissociated cell cultures of fetal rat ventral mesencephalon. Release evoked by all three agonists was Ca2(+)-dependent and inhibited by broad-spectrum antagonists (D,L-cis-2,3-piperidine dicarboxylic acid [PDA] and kynurenic acid [KYN]). However, both of these antagonists were more potent against KAIN than against QUIS and only KAIN-evoked release was blocked by gamma-D-glutamyl-aminomethyl sulfonic acid (GAMS, IC50 700 microM). NMDA-stimulated [3H]DA release was selectively inhibited by competitive (3-[2-carboxypiperazine-4-yl]propyl-1-phosphonic acid [CPP] and D,L-2-amino-5-phosphonovaleric acid [APV]) and non-competitive (phencyclidine and MK-801) NMDA receptor antagonists. In 1.2 mM Mg2+, NMDA-stimulated [3H]DA release was Na(+)-dependent and inhibited by tetrodotoxin (TTX, 2 microM) or by the local anaesthetic, lidocaine (200 microM). However, in 0 Mg 2+, NMDA-evoked release was not inhibited by TTX or lidocaine. Thus, TTX-sensitivity of the NMDA response in 1.2 mM Mg2+ apparently occurs because Na(+)-action potentials are required to alleviate a Mg2+ blockade. Neither QUIS- nor KAIN-evoked release was affected by Mg2+ or TTX. When extracellular NaCl was replaced by sucrose or Na2SO4, the QUIS response was increased. KAIN-evoked release was unaffected by the sucrose substitution and was attenuated in the Na2SO4-containing buffer. It is concluded that NMDA and QUIS/KAIN release [3H]DA via separate receptor subtypes.

Animals↗
PubMed1990

Cholecystokinin antagonists proglumide, lorglumide and benzotript, but not L-364,718, interact with brain opioid binding sites.

It has been reported that proglumide and L-364,718 potentiate opioid-induced antinociception. However, their mode of action in pain modulation is still not understood. To evaluate a possible interaction with opioid receptors, we determined the affinities of the CCK antagonists proglumide, lorglumide, benzotript and L-364,718 on mu, delta and kappa binding sites, using guinea pig brain crude synaptosome preparations. These affinities were compared to that of the central CCK binding site, using rat brain slide-mounted sections. At 100 microM, proglumide competed for 13% and 17% of mu and kappa binding sites, but did not interact with delta and CCK sites. At this concentration, lorglumide reduced mu, delta, kappa and CCK specific binding by 44%, 69%, 35% and 88%, whereas benzotript diminished it by 16%, 13%, 38% and 48%, respectively. L-364,718 did not interact with opioid receptors (assay limit of solubility, 10 microM) but had a high affinity for CCK binding sites (IC50, 126nM). The lack of selectivity of proglumide, lorglumide and benzotript for CCK receptors suggests that their reported ability to potentiate morphine analgesia may be related to an interaction with opioid receptors.

Animals↗
PubMed1990

Quantitative radioautographic study of somatostatin receptors heterogeneity in the rat extrahypothalamic brain.

The possible heterogeneity of extrahypothalamic somatostatin receptors was studied in rat brain by quantitative radioautography. The respective distribution and relative proportion of two somatostatin receptor sub-types (SS1 and SS2) were assessed by using two radioligands, the non-selective probe [125I]Tyr3-D-Trp8-somatostatin14 and the SS1 selective analogue [125I]Tyr3-SMS 201-995. For both ligands, adjacent brain sections were processed in the presence of micromolar concentrations of either a non-discriminative competitor (somatostatin14) or SS1-selective analogue (SMS 201-995). The comparative analysis of the specific binding remaining in the presence of each non-radioactive competitor permitted a semi-quantitative analysis of the proportion of SS1 and SS2 receptor sub-types in each brain region examined. Data obtained correlate well with homogenate binding results reported previously [Reubi J. C. (1984) Neurosci. Lett. 49, 259-263]. Although the distribution patterns obtained with both radioligands were similar, [125I]Tyr3-SMS 201-995 labelled only a fraction of [125I]Tyr0-D-Trp8-somatostatin14-labelled sites in certain brain regions. For example, both superficial and deep cortical laminae, as well as the basolateral amygdaloid nucleus and CA1 hippocampal area exhibited different binding densities with [125I]Tyr0-D-Trp8-somatostatin14 depending on the competitor used in the assay (somatostatin14 or SMS 201-995). On the other hand, [125I]Tyr3-SMS 201-995 binding was eliminated in an identical fashion by either competitor in these very same brain areas. This suggests the existence of SS1 and SS2 somatostatin receptor sub-types in these regions. In all other brain areas examined, somatostatin receptor sites are apparently of the SS1 sub-type. The heterogeneity of somatostatin receptors observed in certain regions may have relevance for the various biological effects induced by somatostatin in the central nervous system.

Animals↗
PubMed1990

Quantitative autoradiographic distribution of [125I]Bolton-Hunter neuropeptide Y receptor binding sites in rat brain. Comparison with [125I]peptide YY receptor sites.

The autoradiographic distribution of [125I]Bolton-Hunter neuropeptide Y receptor binding sites was quantified in rat brain. The highest level of [125I]Bolton-Hunter neuropeptide Y binding sites was seen in the hippocampus (ventral stratum radiatum, CA3 subfield: 6029 +/- 250 fmol/g tissue). The distribution of these sites was clearly laminated, being particularly concentrated in the oriens layer (dorsal CA3 subfield: 2562 +/- 147 fmol/g tissue) and stratum radiatum (dorsal CA3 subfield: 2577 +/- 95 fmol/g tissue). Lower levels of sites were seen in the pyramidal cell layer (1708 +/- 105 fmol/g tissue) and the molecular layer (1155 +/- 116 fmol/g tissue). The cortical distribution of [125I]Bolton-Hunter neuropeptide Y receptor sites was also laminated, being particularly enriched in superficial laminae (occipital cortex, layers I-II, 4038 +/- 148 fmol/g tissue; layers III-IV, 1392 +/- 97 fmol/g tissue and layers V-VI, 1522 +/- 138 fmol/g tissue). Other areas containing high amounts of sites included the anterior olfactory nuclei (ventral part, 4935 +/- 119 fmol/g tissue; lateral part, 4530 +/- 149 fmol/g tissue; dorsal part, 3378 +/- 140 fmol/g tissue and medial part, 2601 +/- 150 fmol/g tissue); anteromedial (5168 +/- 211 fmol/g tissue), medial (4611 +/- 107 fmol/g tissue) and lateral posterior thalamic nuclei (4465 +/- 189 fmol/g tissue); medial mammillary nucleus (5555 +/- 241 fmol/g tissue); medial geniculate nucleus (4747 +/- 56 fmol/g tissue); claustrum (4123 +/- 235 fmol/g tissue); posteromedial cortical amygdaloid nucleus (3524 +/- 138 fmol/g tissue), tenia tecta (2540 +/- 195 fmol/g tissue); lateral septum (1785 +/- 90 fmol/g tissue); suprachiasmatic hypothalamic nucleus (1604 +/- 115 fmol/g tissue), and substantia nigra, pars compacta (1846 +/- 142 fmol/g tissue) and pars lateralis (1750 +/- 165 fmol/g tissue). Areas moderately enriched with [125I]Bolton-Hunter neuropeptide Y binding sites included the zonal layer of the superior colliculus (1347 +/- 71 fmol/g tissue); anterior pretectal nucleus (1172 +/- 113 fmol/g tissue); ventral tegmental area (1090 +/- 97 fmol/g tissue); periventricular fibre system (1026 +/- 48 fmol/g tissue); core of nucleus accumbens (948 +/- 29 fmol/g tissue) and area postrema (799 +/- 87 fmol/g tissue). These results are discussed with regard to some of the suggested biological effects of neuropeptide Y in the central nervous system such as effects on learning, locomotion and circadian rhythms. Moreover, we also compared the distribution of [125I]Bolton-Hunter neuropeptide Y receptor sites with that of [125I]peptide YY sites in rat brain. The resolution of the autoradiographic image is better with [125I]peptide YY most likely because of higher affinity and percentage of specific labelling.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Structural study of the N-terminal segment of neuropeptide tyrosine.

A series of analogues of neuropeptide tyrosine (NPY) was synthesized by solid-phase peptide synthesis using BOP as a coupling reagent for the complete synthesis. A structure-activity study of the N-terminal portion of the molecule was performed with the analogues obtained by the successive replacement of the first 10 amino acids by the residue L-alanine. NPY and its analogues [Ala1-10]hNPY were tested for their potency on rat vas deferens and for their affinity to central nervous system receptors on a rat brain membrane preparation. The results suggest that the hypothetical polyproline type II helix structure of the N-terminal segment is involved in both potency and affinity. Indeed, the substitution by L-Ala of proline residues in position 2, 5, or 8 showed important losses of activity and affinity. The more important losses were observed with the replacement of Pro-5 or Pro-8. A critical loss of potency of hNPY was also observed after the substitution of the Tyr-1 residue by L-Ala, thus confirming the important role played by this residue for the full expression of the biological activity of NPY.

Alanine↗
PubMed1990

gamma-Preprotachykinin-(72-92)-peptide amide: an endogenous preprotachykinin I gene-derived peptide that preferentially binds to neurokinin-2 receptors.

The presence of N-terminally extended forms of neurokinin A has recently been reported in the mammalian brain. Among them, gamma-preprotachykinin-(72-92)-peptide amide [gamma-PPT-(72-92)-NH2], a peptide derived by posttranslational processing of gamma-preprotachykinin, is most prominent. We report here that this peptide most likely acts on neurokinin-2 receptor sites since neurokinin A (a putative neurokinin-2 agonist) and gamma-PPT-(72-92)-NH2 are potent competitors of 125I-labeled gamma-PPT-(72-92)-NH2 binding whereas selective neurokinin-1 and -3 agonists are not. Moreover, the distribution of 125I-labeled gamma-PPT-(72-92)-NH2 and 125I-labeled neurokinin A binding sites are very similar in rat brain. On the other hand, 125I-labeled Bolton-Hunter-substance P (a neurokinin-1 ligand) and 125I-labeled Bolton-Hunter-eledoisin (a neurokinin-3 ligand) binding sites are differentially located in this tissue. Thus, it appears that gamma-PPT-(72-92)-NH2 binds to neurokinin-2 receptors and should be considered as a putative endogenous ligand for this receptor class.

Animals↗
PubMed1990

Neurochemical deficits in pathological brain aging: specificity and possible relevance for treatment strategies.

Normal brain aging is accompanied by the losses of certain neuronal populations and the appearance of structures such as neuronal plaques and neurofibrillary tangles. Additionally, various neurotransmitter systems are altered in the elderly, although marked variations are observed between individuals, suggesting important differences between successful and unsuccessful aging. In certain pathological conditions, only certain features of normal aging are exacerbated. For example, the densities of forebrain cholinergic neurons are markedly decreased in cortical and hippocampal (but not striatal) areas in Alzheimer's disease. We discuss here the comparative alterations of cholinergic markers in certain neurological disorders such as Alzheimer's disease, Parkinson's disease, and the combined pathology. Differential alterations of brain cholinergic profile are observed in each disorder, this most likely having functional significance. We also found that muscarinic receptors of the M2 subtype act as negative autoreceptors to decrease brain acetylcholine release, whereas nicotinic agonists induced the opposite effect. This suggests that blockade of negative M2 or stimulation of positive nicotinic autoreceptors could have beneficial effects in Alzheimer's disease. Additionally, modulation of heteroreceptor activation such as the serotonergic or interleukin-2 sites located on or in proximity to cholinergic nerve terminals could offer alternate strategies for the treatment of cholinergic deficits in pathological brain aging.

Aging↗
PubMed1990

Neurotensin regulation of endogenous acetylcholine release from rat cerebral cortex: effect of quinolinic acid lesions of the basal forebrain.

The effects of neurotensin (NT) on endogenous acetylcholine (ACh) release from basal forebrain, frontal cortex, and parietal cortex slices were tested. The results show that NT differentially regulates evoked ACh release from frontal and parietal cortex slices without altering either spontaneous or evoked ACh release from basal forebrain slices. In the frontal cortex, NT significantly inhibited evoked ACh release by a tetrodotoxin (TTX)-insensitive mechanism, suggesting an action directly on cholinergic terminals. In the parietal cortex, NT enhanced evoked ACh release by a TTX-sensitive mechanism, suggesting an action of NT on the cholinergic neuron or in close proximity to the cholinergic neuron. The effects of NT on ACh release were confined to evoked ACh release; that is, spontaneous ACh release was not affected. NT did not affect spontaneous or potassium-evoked ACh release from occipital cortex slices. The second set of experiments tested the effects of quinolinic acid (QUIN) lesions of the basal forebrain cell bodies on the NT-induced regulation of evoked ACh release in the cerebral cortex. QUIN lesions of basal forebrain cell bodies caused decreases in choline acetyltransferase activity (27 and 28%), spontaneous ACh release (14 and 21%), and evoked ACh release (38 and 44%) in frontal and parietal cortex, respectively. In addition, 11 days following QUIN lesions of basal forebrain cell bodies, the action of NT to regulate evoked ACh release in frontal cortex or parietal cortex was no longer observed. The results suggest that in the rat frontal and parietal cortex, NT differentially regulates the activity of cholinergic neurons by decreasing and increasing evoked ACh release, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1990

Evidence that somatostatin enhances endogenous acetylcholine release in the rat hippocampus.

The present experiments show that somatostatin (SS)-like immunoreactive material is present in the hippocampus and that its release can be increased by K+ stimulation of rat hippocampal slices, suggesting that SS-like peptides may be of significance to neurotransmission in the hippocampus. Exogenous SS-28 and SS-14 enhanced the K(+)-evoked release of endogenous acetylcholine (ACh) from rat hippocampal slices, whereas amino-terminal fragments of SS-28 did not. The increased ACh release in the presence of either peptide appeared to be mediated by an interaction with SS receptors because cyclo-SS, a putative SS antagonist, abolished the effects of both SS-28 and SS-14. In addition, the increase in ACh release induced by SS-14 or SS-28 was antagonized by the calcium channel antagonists omega-conotoxin GVIA, nifedipine, and cinnarizine, implicating voltage-sensitive calcium channels in this effect. Moreover, the effect was sensitive to tetrodotoxin, suggesting an indirect action of the peptides at a site distal to cholinergic nerve terminals. Cysteamine, which has been reported to deplete SS content and to increase SS release in brain, augmented the basal and evoked release of ACh from hippocampal slices, without affecting SS-like content and release. Finally, neuropeptide Y, which is colocalized with SS in many neurons of the hippocampal formation, did not alter ACh release, nor did it facilitate the SS-induced increase. The results suggest that in the rat hippocampus, both SS-28 and SS-14 interact with SS receptors to regulate ACh release indirectly by a mechanism that involves alterations of calcium influx during depolarization.

Acetylcholine↗