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Biomedical subjects

R D Pinnock

Publications and source records attributed to R D Pinnock.

69 records · Page 4Linked to original sources
PubMed1984

Neurotensin stimulates inositol phospholipid hydrolysis in rat brain slices.

Neurotensin stimulated inositol phospholipid hydrolysis in matched coronal vibratome sections through the rat brain. This effect was tetrodotoxin-resistant and a good correlation was noticed between the magnitude of neurotensin-stimulated inositol phospholipid hydrolysis and the number of specific [3H]neurotensin binding sites in various brain regions. Neurotensin produced no significant effect on either basal or stimulated cAMP levels.

Animals↗
PubMed1984

Hyperpolarizing action of baclofen on neurons in the rat substantia nigra slice.

GABA, muscimol and L-baclofen inhibited zona compacta neurons in the rat substantia nigra slice, D-baclofen was inactive, L-baclofen produced a potent hyperpolarization of the membrane potential. The actions of muscimol but not GABA and L-baclofen were reversed by bicuculline. The actions of muscimol and baclofen are likely to be mediated by interactions with two different receptors.

Animals↗
PubMed1984

The actions of antipsychotic drugs on dopamine receptors in the rat substantia nigra.

The activity of neurones in the zona compacta of the rat substantia nigra was recorded extracellularly in vitro. Dopamine produced a dose-dependent depression of firing, threshold doses being in the 3 microM range. The inhibitory effects of dopamine were antagonized by (-)-sulpiride (pA2 7.5), haloperidol (pA2 8.4) and cis-flupenthixol (pA2 6.9). The actions of gamma-aminobutyric acid (GABA) were not affected by these compounds. The gradients of Schild plots of data for (-)-sulpiride were less than unity while those for haloperidol and cis-flupenthixol were greater than unity, which suggests that the antagonism was not competitive. This is discussed with regard to the use of a bioassay system in the analysis of the effects of antagonists. Haloperidol and (-)-sulpiride were found to have similar potencies, as dopamine receptor antagonists, to those predicted from biochemical and clinical efficacy studies, but cis-flupenthixol was less potent than expected.

Action Potentials↗
PubMed1983

Sensitivity of compacta neurones in the rat substantia nigra slice to dopamine agonists.

Extracellular recordings were made from neurones in the zona compacta of the substantia nigra in a novel slice preparation in vitro. The pharmacological profile of some dopamine related drugs was assessed by their depressant action on neuronal firing after known concentrations were added to the perfusing media. The most potent drugs were the rigid stable dopamine analogues 2-amino-6,7-dihydroxy-1,2,3,4- tetrahydronapthalene (ADTN) and apomorphine. 2-Amino-5,6-dihydroxy-1,2,3,4- tetrahydronapthalene (5,6-ATN), was less potent than either. Octopamine, Norphenephrine , m- and p-tyramine were all less potent than dopamine. Although noradrenaline was equipotent to dopamine, alpha- and beta-adrenoreceptors were not involved since propranolol and phentolamine were not antagonists, while (-)-sulpiride, haloperidol and alpha-flupentixol were potent antagonists of the dopamine mediated responses.

Animals↗
PubMed1983

Substance P excitation of rat locus coeruleus neurones.

We have made extracellular recordings from locus coeruleus neurones contained in a pontine slice preparation. The in vitro technique permits application of known concentrations of drugs in the perfusion medium. Substance P excites locus coeruleus neurones in a concentration-dependent manner. The activity of substance P was found to reside in the C terminal region of the molecule. The relative potency of substance P and related peptides suggests that the substance P receptors present within the locus coeruleus are predominately of the substance P-P type. The synthetic analogue [D-Pro2,D-Trp7.9]substance P was not found to antagonise the action of substance P on locus coeruleus neurones.

Animals↗
PubMed1983

Actions of substance P, MIF, TRH and related peptides in the substantia nigra, caudate nucleus and nucleus accumbens.

Neurones in the substantia nigra were found to be sensitive to iontophoretically applied substance P, substance P 1-9 methyl ester and substance P 1-9 amide. Substance P 1-2, 4-9 and 5-9 methyl esters, thyrotropin releasing hormone (TRH), Pyroglutamyl-histidyl-2 methyl prolineamide (methyl TRH), Pyroglutamyl-histidyl-2 methyl prolineamide (methyl TRH), histidyl-proline-diketopiperazine (His-Pro) and MSH releasing inhibiting factor (MIF) were without effect on neurones in this area. Thyrotropin releasing hormone (TRH), methyl TRH, His-Pro and MIF were inactive on neurones in the caudate nucleus and nucleus accumbens. Bilateral injections of substance P and substance P 1-9 methyl ester into the ventral tegmental area (VTA) of conscious rats produced locomotor activity, while similar injections of substance P 4-9 and 5-9 methyl esters did not. The locomotor activity produced by amphetamine was prolonged by TRH, while MIF was devoid of such activity. The data suggest that substance P and substance P 1-9 have similar effects in the substantia nigra, although the mechanism of action is unclear. Thyrotropin releasing hormone and MIF probably do not have acute actions in the brain areas tested.

Animals↗
PubMed1983

A comparison of the release of substance P and some synthetic analogues from micropipettes by microiontophoresis or pressure.

The release of substance P (SP) and two analogues by iontophoresis or pressure from microelectrodes was compared. Substance P was released linearly by iontophoresis from electrodes while no release of the analogues was detected. [N-methylphenylalanine8, N-methylglycine9-] SP5-11 (DiMeC7) and [methyl-2-aminoethyl]11 SP (SP-DAE) were released from electrodes by pressure ejection with linear relationships in all cases between pressure and the amounts released. Under the tested experimental conditions, release of substance P by iontophoresis was between 2 and 3 orders of magnitude less than that by pressure over a given time. The release of substance P and the uncharged analogue DiMeC7 by pressure was very similar while release of SP-DAE was one order of magnitude less.

Electrophoresis↗
PubMed1982

Differential sensitivity of presumed dopaminergic and non-dopaminergic neurones in rat substantia nigra to electrophoretically applied substance P.

Substance P (SP) was administered by microelectrophoresis to physiologically identified substantia nigra neurones in halothane anaesthetized rats. Dopaminergic neurones of the substantia nigra compacta (SNC) were markedly less sensitive to SP than non-dopaminergic cells of the substantia nigra reticulata (SNR) when the peptide was administered with the same micropipettes. Identified substantia nigra neurones were also differentially sensitive to other putative transmitters including dopamine, 5-HT and acetylcholine. No interactions could be demonstrated between SP and the responses to other transmitters.

Acetylcholine↗
PubMed1982

Substance P receptors in the nervous system and possible receptor subtypes.

The ability of various related peptides and substance P analogues to compete for the binding of 3H-labelled substance P to rat brain membranes corresponds with their known biological activities, providing a simple model for studies of peptide receptors in the central nervous system. In salivary gland and brain slices substance P and related peptides stimulate the rate of incorporation of phosphatidylinositol, offering an alternative biochemical model for substance P receptor studies. Two types of receptor may be responsible for the actions of substance P on peripheral tissues: the SP-P type, where all tachykinins are approximately equally active, and the SP-E type, where eledoisin and kassinin are more potent than the other tachykinins. Alkyl esters of substance P appear to act as selective SP-P agonists.

Animals↗
PubMedDate not supplied

Correlation between inositol phospholipid hydrolysis and substance P receptors in rat CNS.

The undecapeptide substance P is a neurotransmitter candidate in the mammalian central and peripheral nervous system. Although the distribution of substance P-like immunoreactivity within the central nervous system (CNS) is well established, the recent identification and autoradiographic localization of specific substance P-binding sites has revealed numerous areas of mismatch between peptide levels and numbers of such sites. Previous studies have shown that substance P stimulates the hydrolysis of inositol phospholipids in peripheral tissues and in the hypothalamus, probably through stimulation of a polyphosphoinositide-specific phospholipase C (refs 9-11). Inositol phospholipid hydrolysis has been implicated in the mobilization of cytosolic calcium following receptor activation in several neurotransmitter and hormonal systems. We have therefore investigated the distribution of 3H-labelled substance P binding sites within various rat brain regions and correlated this with the rate of substance P-induced hydrolysis of inositol phospholipids in the same areas of the CNS. We found that the rate of inositol phospholipid hydrolysis was proportional to the number of binding sites specific for 3H-substance P, suggesting that binding sites revealed by 3H-substance P autoradiography correspond to functional substance P receptors.

Animals↗