Substance P as a neuromodulator of cerebellar cholinergic systems

Vlasova, I. G.; Dolgopol’skii, A. L.

doi:10.1007/bf02688171

Cited by 2 publications

(2 citation statements)

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“…Acetylcholine (ACh) is one of the key transmitters in cognitive processes (for recent reviews, see Deiana et al, 2011, Graef et al, 2011, Micheau and Marighetto, 2011, and many putative substrates of PREP are involved in the regulation of cholinergic neurotransmission. For example, increased levels of TRH (Toide et al, 1993) and SP (Perez et al, 2007, Vlasova andDolgopol'skii, 2000) have been shown to increase ACh efflux in the rat brain. However, little is known about the effects of PREP inhibitors on brain ACh levels.…”

Section: Introductionmentioning

confidence: 99%

The effect of prolyl oligopeptidase inhibition on extracellular acetylcholine and dopamine levels in the rat striatum

Jalkanen

Piepponen

Hakkarainen

et al. 2012

Neurochemistry International

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Prolyl oligopeptidase (PREP, EC 3.4.21.26) inhibitors have potential as cognition enhancers, but the mechanism of action behind the cognitive effects remains unclear. Since acetylcholine (ACh) and dopamine (DA) are known to be associated with the regulation of cognitive processes, we investigated the effects of two PREP inhibitors on the extracellular levels of ACh and DA in the rat striatum using in vivo microdialysis. KYP-2047 and JTP-4819 were administered either as a single systemic dose (50 μmol/kg∼17 mg/kg i.p.) or directly into the striatum by retrodialysis via the microdialysis probe (12.5, 37.5 or 125 μM at 1.5 μl/min for 60 min). PREP inhibitors had no significant effect on striatal DA levels after systemic administration. JTP-4819 significantly decreased ACh levels both after systemic (by ∼25%) and intrastriatal (by ∼30-50%) administration. KYP-2047 decreased ACh levels only after intrastriatal administration by retrodialysis (by ∼40-50%) when higher drug levels were reached, indicating that higher brain drug levels are needed to modulate ACh levels than to inhibit PREP. This result does not support the earlier hypothesis that the positive cognitive effects of PREP inhibitors in rodents would be mediated through the cholinergic system. In vitro specificity studies did not reveal any obvious off-targets that could explain the observed effect of KYP-2047 and JTP-4819 on ACh levels, instead confirming the concept that these compounds have a high selectivity towards PREP.

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Section: Introductionmentioning

confidence: 99%

The effect of prolyl oligopeptidase inhibition on extracellular acetylcholine and dopamine levels in the rat striatum

Jalkanen

Piepponen

Hakkarainen

et al. 2012

Neurochemistry International

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“…Because it is well known that dorsal root ganglia project to pelvic viscera via pelvic nerves (de Groat et al 1983) it is also likely that some SP-IR sensory neurons make functional synapses with CART-IR pelvic ganglia neurons. Interestingly, in the central nervous system SP was found to mediate the activity of both cholinergic (Vlasova and Dolgopol'skii 2000) and noradrenergic neurons (Ebner and Singewald 2007), but whether such action is also present in relation to peripheral PP is a matter of speculation only. In conclusion, in the present work we have identified and described for the first time CART-like immunoreactivity in elements of PP in the female pig.…”

Section: Discussionmentioning

confidence: 99%

Distribution and immunohistochemical characteristics of cocaine- and amphetamineregulated transcript-positive nerve elements in the pelvic ganglia of the female pig

Zacharko-Siembida¹,

Matysek²,

Szalak³

et al. 2017

Polish Journal of Veterinary Sciences

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Cocaine-and amphetamine-regulated transcript (CART) peptides are widely expressed not only in the brain but also in numerous endocrine/neuroendocrine cells as well as in neurons of the peripheral nervous system. The present study investigated the distribution patterns of CART-like immunoreactivity in the pelvic plexus (PP) of the female pig. The co-expression of CART with principal neurotransmitter markers: choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), serotonin (5-HT) or biologically active neuropeptides: pituitary adenylate cyclase-activating polypeptide (PACAP), substance P (SP), calbindin was analyzed using double immunohistochemical stainings. Amongst neurons immunopositive to Hu C/D panneuronal marker as many as 4.1 ± 1.2% in right and 4.4 ± 1.6% in left pelvic ganglia were found to express CART. The vast majority of CART-IR ganglionic neurons were predominantly small in size and were evenly scattered throughout particular ganglia. Immunoreactivity to CART was also detected in numerous nerve terminals (which frequently formed pericellular formations around CART-negative perikarya) as well as in numerous nerve fibres within nerve branches interconnecting the unilateral pelvic ganglia. Immunohistochemistry revealed that virtually all CART-IR neurons were cholinergic in nature and CART-IR basket-like formations frequently encircled TH-positive/CART-negative perikarya. None of CART-IR ganglionic neurons showed immunoreactivity to SP, PACAP, 5-HT or calbindin. CART-IR nerve fibres ran in a close vicinity to serotonin-containing cells or faintly labelled SP-expressing neurons. On the other hand, PACAP-IR, SP-IR (but not 5-HT-positive) nerve terminals were found to run in close proximity to CART-IR neurons. Our results indicate that: 1) CART present in PP may influence the activity of pelvic ganglionic neurons/SIF cells, 2) PP should be considered as a potential source of CART-like supply to pelvic viscera and 3) functional interactions between CART and SP or PACAP are possible at the periphery.

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Substance P as a neuromodulator of cerebellar cholinergic systems

Cited by 2 publications

References 3 publications

The effect of prolyl oligopeptidase inhibition on extracellular acetylcholine and dopamine levels in the rat striatum

The effect of prolyl oligopeptidase inhibition on extracellular acetylcholine and dopamine levels in the rat striatum

Distribution and immunohistochemical characteristics of cocaine- and amphetamineregulated transcript-positive nerve elements in the pelvic ganglia of the female pig

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