Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. 5-Hydroxytryptamine (5-HT) receptor-mediated contraction of endothelium denuded rabbit middle (MCA) and posterior (PCA) cerebral arteries was characterized by use of selective agonists and antagonists for different 5-HT receptor subtypes. 2. 5-HT and various 5-HT receptor agonists contracted the arteries with the following rank order of potency in MCA: 5-carboxamidotryptamine (5-CT) > 5-HT > 5-methoxytryptamine (5-MeOT) > sumatriptan > alpha-methyl-5-HT (alpha-Me-5-HT) >> 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and in PCA: 5-CT > 5-HT > sumatriptan > 5-MeOT > alpha-Me-5-HT >> 8-OH-DPAT. With few exceptions, the maximal contractile responses of these agonists were similar to that induced by 5-HT. 3. The selective antagonists of 5-HT2A/2C (ketanserin), 5-HT4 (SDZ 205-557) and 5-HT1A/1B (S-(-)-propranolol) sites were devoid of inhibitory effect on 5-HT-mediated contraction in both MCA and PCA, thus excluding activation of the corresponding receptors. 4. In both arteries, the contraction-response curve to 5-HT was unaffected by the 5-HT3 receptor antagonist, ICS 205-930 (0.01 and 0.1 microM) whilst a small (3 and 6 fold displacement) was seen with MDL 72222 (0.1 and 1 microM). 5. The mixed 5-HT1-like/5-HT2A receptor antagonist, methiothepin (0.001-0.1 microM), was a potent antagonist of 5-HT-induced contractions in both arteries, giving pA2 values of 9.4 +/- 0.7 and 9.6 +/- 0.8 in MCA and PCA, respectively. 6. Rauwolscine (O.1-10 MicroM) and yohimbine (0.3, 3 MicroM) inhibited contractions to 5-HT in a competitive manner, pA2 values of 7.1 +/- 0.6 and 6.7 +/-0.6 were determined for rauwolscine in MCA and PCA,respectively. An apparent pA2 value of 6.9 +/-0.2 was calculated for yohimbine (3 MicroM) in both MCA and PCA.7. In conclusion, these results suggest that the contractile response to 5-HT in rabbit isolated MCA and PCA is predominantly mediated by the 5-HTID receptor subtype, although a small contribution by 5-HT3 receptors cannot be excluded.
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PMID:Mediation by 5-HT1D receptors of 5-hydroxytryptamine-induced contractions of rabbit middle and posterior cerebral arteries. 792 24

A previous report has shown that small diameter serotoninergic (5-HT) axons innervating the forebrain are selectively eliminated by treatment with an amphetamine derivative, (+/-)p-chloroamphetamine (PCA; Mamounas et al., [1991] J. Comp. Neurol. 314:558-586). It is well known that the spinal cord is the target of numerous monoaminergic fibers of different types. We have previously shown that the dorsal and ventral horns and the intermediolateral cell column are innervated by numerous serotonin-, noradrenaline- and dopamine-containing axons, including both thin axons with small varicosities and beaded axons with large varicosities. In all these regions, the large majority of fine indolaminergic fibers do not establish synaptic contacts, contrasting with the beaded axons which mostly exhibit synapses. The present work was conducted to study the effect of PCA on the monoaminergic innervation of the adult rat spinal cord. Animals received two subcutaneous doses of PCA 24 hours apart and were perfused 3 weeks later. Immunocytochemistry was performed to detect 5-HT, noradrenergic and dopaminergic fibers by using light and electron microscopy. Light microscopy revealed that PCA treatment caused a marked and selective elimination of the fine 5-HT-immunoreactive fibers, mainly found in the dorsal horn, but spared all other larger axons. This selective effect on the dorsal horn innervating thin 5-HT fibers was confirmed with the electron microscope by calculating the synaptic incidence(s) of monoaminergic innervation. These results suggest that fine and beaded 5-HT axons correspond to two anatomically, biochemically and pharmacologically different types of fibers, which could arise from two subpopulations of brainstem neurons. In addition, this drug could be used to provide an experimental animal, devoid of 5-HT nonsynaptic fibers, thereby facilitating a study on the role of dorsal horn nonsynaptic system in pain modulation.
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PMID:Light and electron microscopic studies of the effects of p-chloroamphetamine on the monoaminergic innervation of the rat spinal cord. 802 44

The potential roles of central and peripheral 5-HT3 receptors in the secretion of prolactin, adrenocorticotropic hormone (ACTH), corticosterone and renin was investigated. Male rats received the 5-HT3 antagonist ondansetron (0, 0.1 or 1 mg/kg i.p.), 30 min prior to injections of the serotonin (5-HT) releaser, p-chloroamphetamine (PCA; 0, 3 or 8 mg/kg i.p.). Blood samples were collected 60 min after PCA for radioimmunoassays of plasma prolactin, ACTH, corticosterone and renin concentrations. PCA significantly elevated secretion of each of these hormones. Pretreatment with the 5-HT3 antagonist, ondansetron, significantly attenuated the PCA-induced elevation of prolactin secretion, suggesting that 5-HT3 receptors contribute to the serotonergic stimulation of prolactin secretion. Ondansetron did not modify effects of PCA on ACTH, corticosterone or renin secretion. To determine whether the 5-HT3 receptor role in prolactin secretion is mediated in the brain, the endocrine effects of intracerebroventricular (i.c.v.) injections of 5-HT (30 micrograms/kg) or the 5-HT3 agonist, 2-methylserotonin (1, 20 or 200 micrograms/kg) were evaluated. Both 5-HT and 2-methylserotonin significantly elevated plasma prolactin levels 15 min postinjection. However, ondansetron (1 mg/kg i.p.) did not antagonize these actions. Both 5-HT and 2-methylserotonin also increased plasma ACTH and corticosterone concentrations. Finally, 5-HT suppressed, while 2-methylserotonin stimulated renin secretion. None of the hormonal effects of i.c.v. injected 5-HT or 2-methylserotonin were altered by ondansetron. Thus, the results suggest that peripheral, but not central 5-HT3 receptors are involved in the stimulation of prolactin secretion. Furthermore, 5-HT3 receptors do not mediate the serotonergic stimulation of ACTH, corticosterone, or renin secretion.
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PMID:Investigation of the role of 5-HT3 receptors in the secretion of prolactin, ACTH and renin. 826 57

In adult rats, methamphetamine produces biochemical alterations in brain serotonin (5-HT) neurons. Since 5-HT is critical to the development of fetal 5-HT neurons and target tissues, we hypothesized that in utero exposure to methamphetamine could result in long-term alterations in postnatal 5-HT systems. Pregnant Sprague-Dawley rats, administered either saline or (+/-)methamphetamine (5 mg/kg, s.c., b.i.d.) from gestational day 13 to 20, were divided into three treatment groups: Saline-injected/Ad Lib Fed (VEH); Saline-injected/Pair Fed (PF); and methamphetamine injected (METH). Prenatal methamphetamine exposure did not alter litter size, gender number, or progeny birth weights. Functional alterations in serotonergic systems were determined in postnatal day (PD) 70 male progeny and in PD 30 female progeny by measuring changes in 5-HT mediated increases in plasma hormones following a single injection of the 5-HT releaser p-chloroamphetamine (PCA; 8 mg/kg). Prenatal methamphetamine produced long-term marked (-30 to -62%) attenuation of plasma renin responses to PCA in male and female progeny. In contrast, no alterations were observed in the ACTH, corticosterone, or prolactin responses to PCA in male and female progeny. Prenatal methamphetamine did not alter basal levels of any hormones measured regardless of gender. No significant differences were observed in the density of cortical or hypothalamic 5-HT uptake sites, or in the density of cortical 5-HT1 or 5-HT2 receptors in male progeny. The lack of significant differences in cortical 5-HT uptake sites observed between PF and METH treated dams 2 days post-parturition indicates that methamphetamine was not neurotoxic to the pregnant dams. These data, which demonstrate longterm postnatal deficits in 5-HT mediated renin secretion, suggest selective functional alterations of brain 5-HT systems in male and female progeny exposed in utero to methamphetamine.
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PMID:Prenatal methamphetamine attenuates serotonin mediated renin secretion in male and female rat progeny: evidence for selective long-term dysfunction of serotonin pathways in brain. 827 97

Dark Agouti rats injected with either p-chloroamphetamine (PCA; 2.5 mg/kg i.p.) or fenfluramine (15 mg/kg i.p.) had substantial decreases (approximately 50%) in the concentration of 5-HT and 5-HIAA and binding of [3H]paroxetine in the cerebral cortex 7 days later. This indicates that both compounds had produced neurodegeneration of 5-HT axon terminals. Two doses of alpha-phenyl-N-tert-butyl nitrone (PBN; 150 mg/kg i.p.) 130 min apart had no effect on cortical 5-HT content or [3H]paroxetine binding. However, when PBN (150 mg/ kg) was given 10 min before and 120 min after PCA (2.5 mg/kg) it attenuated the PCA-induced neurodegeneration. In contrast, PBN was without significant effect on the fenfluramine-induced damage. Changes in rectal temperature following either the neurotoxins or neurotoxins+ PBN were no more than +/-1 degree C of saline-injected control rats. These data indicate that PCA, like MDMA, probably induces neurotoxic degeneration because of the formation of catechol or quinone metabolites and subsequent reactive tree radical formation. Such a mechanism does not appear to explain fenfluramine-induced damage to 5-HT neurones.
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PMID:The spin trap reagent PBN attenuates degeneration of 5-HT neurones in rat brain induced by p-chloroamphetamine but not fenfluramine. 902 9

We have previously reported that neonatal (P3) serotonin (5-HT) depletion results in a significant decrease in the number of dendritic spines per 50 microns of dendritic length on dentate granule cells. This effect is specific and permanent. Neither total dendritic length nor the number of dendritic segments is affected by 5-HT depletion. The area dentata contains a dense 5-HT1a receptor population that is present in the at birth. Therefore, 5-HT1a receptors represented a likely candidate for the mediation of the effects of 5-HT on developing granule cells. The present study used the drugs buspirone and NAN-190, which have been shown to be an agonist and antagonist respectively at postsynaptic 5-HT1a receptors in vivo, to test the idea that neurotrophic actions of 5-HT result from 5-HT1a receptor stimulation. Following 5-HT depletion with PCA, pups received daily injections of buspirone (1.0 mg/kg) from P5 to P14. Granule cell morphology was then studied using intracellular filling with Neurobiotin on P14, P21 and P60. Buspirone treatment prevented the loss of dendritic spines previously shown to follow 5-HT depletion with PCA. No other morphological parameters were significantly changed by buspirone treatment. Naive pups received daily injections of NAN-190 from P3 to P14. One group received 1.0 mg/kg while a second group received 3.5 mg/kg. Both doses of NAN-190 resulted in dendritic spine loss comparable to that obtained with neonatal PCA treatment. This loss was permanent suggesting that the first two postnatal weeks may represent a critical period for the action of 5-HT on developing granule cells. Significant, dose-dependent changes in total dendritic length and number of dendritic segments reminiscent of the effects of norepinephrine depletion were also observed in NAN-190-treated rats. We suspect that this change is the result of the action NAN-190 at alpha receptors and is therefore distinct from the specific effect of 5-HT on the number of dendritic spines. The NAN-190 experiment also shows that the loss of dendritic spines is a function of decreased stimulation of 5-HT1a receptors and not the loss of 5-HT terminal membrane.
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PMID:5-HT1a receptors mediate the neurotrophic effect of serotonin on developing dentate granule cells. 905 Dec 59

The effects of post-training (i.p.) injection of TFMPP, mCPP, DOI or 1-NP in the autoshaping learning task was explored. Furthermore, the post-training effects of these agonists after treatment with the antagonists (+/-)-pindolol, (+/-)-propranolol, NAN-190, ketanserin, ritanserin, mesulergine, MDL-72222 or p-chloroamphetamine (5-HT depleter) were studied. Rats were individually trained with a lever-press response (conditioned response; CR) on the autoshaping task and tested 24 h later. The results showed that the injection of TFMPP (1-10 mg/kg), mCPP (1-10 mg/kg), 1-NP (0.1-1.0 mg/kg) or mesulergine (0.4 mg/kg) decreased the rate of CR, while DOI (0.01-0.1 mg/kg) and ritanserin (0.5 mg/kg) and ketanserin (0.001-0.1 mg/kg) increased it. However, the effect induced by TFMPP was reversed by (+/-)-pindolol, ketanserin, ritanserin and PCA; the mCPP-induced effect was antagonized by (+/-)-propranolol, ketanserin, ritanserin and MDL-72222; and the effect produced by 1-NP was reversed by ketanserin, ritanserin and PCA. In addition, the increment in CR provoked by DOI was enhanced by ketanserin, and reversed by ritanserin, mesulergine and PCA. These findings suggest that TFMPP, 1-NP and DOI exerted their effects via stimulation of presynaptic 5-HT receptors. The effects of mCPP most probably reflect activation of postsynaptic receptors. The present data suggest that both 5-HT1B and 5-HT2A-2C receptors play a significant role in the consolidation of learning.
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PMID:Role of 5-HT1B, 5-HT2A and 5-HT2C receptors in learning. 933 78

The effects of gonadal steroids on serotonin (5-HT) synthesis and metabolism in the early developing brain were investigated. Seven-day-old (7 days post-hatch) tilapia, Oreochromis mossambicus were continuously treated with 17beta-estradiol (E2), methyltestosterone (MT) and para-chlorophenylalanine (p-PCA) up to the age of 30 days. The brain 5-HT content, before 30 days, increased with age. The result indicates that this is a developing period of the central 5-HTergic system. During this developing period, the activity of tryptophan hydroxylase (TPH) and monoamine oxidase (MAO) was not altered by age. Both E2 and MT influence the central 5-HT content during its restricted developmental period. E2 has an initial inhibitory effect and then a facilitative effect while MT only has a facilitative effect. The initial inhibitory effect of E2 is mediated by decreasing TPH activity and increasing MAO activity to decrease the 5-HT content. The facilitative effect of both E2 and MT is suppressed by p-CPA.
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PMID:Effects of gonadal steroids on the serotonin synthesis and metabolism in the early developing tilapia brain. 1032 10

Three serotonin (5-HT) neurotoxins, p-chlorophenylalanine (PCPA, 125 and 250 mg/kg, i.p.), p-chloroamphetamine (PCA, 10 mg/kg, i.p.) and 5,7-dihydroxytryptamine (5,7-DHT, 200 microg/rat, i.c.v.) were used to examine whether depletion of central 5-HT has an effect on central dopaminergic (DA) neuronal activities or on prolactin (PRL) secretion. Adult ovariectomized Sprague-Dawley rats primed with estrogen (polyestradiol phosphate, 0.1 mg/rat, s.c.) were treated with one of three neurotoxins and then decapitated in the morning after 3-7 days. Blood sample and brain tissues were collected. The acute effect of PCA (from 30 to 180 min) was also determined. The concentrations of 5-HT, DA and their metabolites, 5-hydroxyindoleacetic acid and 3,4-dihydroxyphenylacetic acid, in the median eminence, striatum and nucleus accumbens were determined by HPLC-electrochemical detection. All three toxins significantly depleted central 5-HT stores by 11-20%. Except for PCPA, neither PCA nor 5,7-DHT had any significant effect on basal DA neuronal activities or PRL secretion. PCA also exhibited an acute effect on the release and reuptake of 5-HT and DA. In summary, depletion of central 5-HT stores to a significant extent for 3-7 days did not seem to affect basal DA neuronal activity and PRL secretion.
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PMID:Effects of serotonin depletion by p-chlorophenylalanine, p-chloroamphetamine or 5,7-dihydroxytryptamine on central dopaminergic neurons: focus on tuberoinfundibular dopaminergic neurons and serum prolactin. 1034 67

Arc (activity regulated, cytoskeleton associated protein) is an effector immediate early gene that is selectively localized in the neuronal dendrites. Elevation of brain 5-HT by the combined administration of the monoamine oxidase inhibitor, tranylcypromine (TCP, 5 mg/kg, i.p.), and the 5-HT precursor L-tryptophan (L-TP, 100 mg/kg, i.p.), increased Arc mRNA abundance in the cingulate, orbital, frontal and parietal cortices as well as in the striatum but a reduction was observed in the CA1 region of the hippocampus. The 5-HT releasing agent p-chloroamphetamine (PCA, 5 mg/kg, s.c.) also increased Arc mRNA in the cortical and striatal areas. Depleting brain 5-HT with the tryptophan hydroxylase inhibitor, p-chlorophenylalanine (pCPA, 300 mg/kg, i.p. for two days), on the other hand, significantly attenuated the increase in Arc mRNA induced by tranylcypromine and L-tryptophan (TCP/L-TP). Pretreatment with the 5-HT2 receptor antagonist ketanserin (2 mg/kg, i.p.) significantly attenuated the effect of TCP/L-TP in the cortex but only partially in striatum and did not affect the reduction in the CA1 region. The 5-HT2 agonist DOI (0.2, 1 and 2 mg/kg, i.p.) dose-dependently increased Arc mRNA abundance in cortical areas with a pattern similar to that of TCP/L-TP and PCA. DOI, however, had much weaker effects on Arc mRNA in the striatum and did not have any significant effect in the CA1, CA3 and the dentate gyms (DG) of the hippocampus. Pretreatment with ketanserin completely blocked the effect of DOI on Arc expression. These data suggest that Arc mRNA expression can be induced in the cortex by increases in extracellular 5-HT and that 5-HT2 receptors play a major part in mediating such effects. Additional 5-HT receptors as well as other neurotransmitters may also be involved, particularly in the striatum and in CA1 subfield of the hippocampus. Overall, our data suggest that expression of Arc mRNA is highly responsive to changes in brain 5-HT functions, and may provide a sensitive marker of postsynaptic 5-HT2(2A and 2C) receptor functions.
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PMID:Serotonergic regulation of mRNA expression of Arc, an immediate early gene selectively localized at neuronal dendrites. 1069 12


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