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L D Leake

Publications and source records attributed to L D Leake.

At least 19 recordsLinked to original sources
PubMed1996

Putative nitric oxide synthase (NOS)-containing cells in the central nervous system of the leech, Hirudo medicinalis: NADPH-diaphorase histochemistry.

The presence and distribution of putative nitric oxide synthase (NOS)-containing cells in whole-mount preparations of the central nervous system of the leech, Hirudo medicinalis, were studied using NADPH-diaphorase (NADPH-d) histochemistry. Specific staining occurred mainly in somata of some central neurones but NADPH-d-reactive branches and terminals were found in peripheral nerves and connectives: neuropile areas were stained weakly or unstained. Intense staining was located in many neurones on the ventral side of the segmental ganglia, including primary sensory neurones, motoneurones and interneurones, and in the anterior root ganglion. The sex ganglia contained some extra NADPH-d-positive cells. Head and tail ganglia and the dorsal side of the segmental ganglia showed less staining. Specific activity was not detected in salivary glands, crop or intestine. Controls using beta-NADPH or nitro blue tetrazolium (NBT) alone or with NBT plus alpha-NADPH, beta-NAD+, beta-NADH or beta-NADP+ did not induce specific staining. A potential NOS inhibitor, 2,6-dichlorophenol-indophenol (DPiP) at 10(-3) M, totally abolished NADPH-d-positive staining. Long-term fixation did not change the pattern of distribution of NADPH-d-positive cells. We conclude that (i) fixative-resistant NADPH-diaphorase is a characteristic marker of 12-15% of neurones in the leech CNS, and (ii) the specific distribution of the putative NOS-containing neurones suggests that NO may be a natural signal molecule in leeches.

Animals↗
PubMed1995

Central and peripheral 5-HT receptors in the leech (Hirudo medicinalis) redefined.

1. 5-Hydroxytryptamine (5-HT) receptors in the Retzius neurones (R cells) and longitudinal body wall muscle strips of the leech H. medicinalis were studied using a range of selective agonists developed for mammalian receptors. 2. All agonists induced hyperpolarisation of R cells: the order of their potency was 5-HT > 5-CT > 2-Me 5HT > alpha-Me-5-HT > > CGS-12066B = 5MeOT > PAPP > Buspirone. This receptor is most like a mammalian 5-HT1C/2 receptor. 3. 5-HT induces relaxation of body wall strips, preceded at higher doses by contraction or an increase in spontaneous contractions. The relaxing effect was best mimicked by 5-CT and alpha-Me-5-HT, suggesting a 5-HT1C/2 receptor. The contractile effect was best mimicked by 5-MeOT suggesting a 5-HT4-like receptor. The overall potency of agonists on the body wall muscle was 5-MeOT > 5-CT > 5-HT > alpha-Me-5-HT > 2-Me 5-HT > PAPP > Buspirone > > CGS-12066B. 4. Results suggest that either the sites of 5-HT action possess several different receptors or the receptors themselves are more complex with multiple properties.

Animals↗
PubMed1995

An unique model for the analysis of neuronal nitric oxide signaling: the leech CNS.

An hypothesis for the presence of nitric oxide synthase (NOS) and the involvement of nitric oxide (NO) in neuronal signaling in the leach (Hirudo medicinalis) CNS is based on (i) the presence of fixative resistant NADPH-diaphorase (NADPH-d) in a specific neuronal population in the segmental ganglion; (ii) direct measurements with NO-sensitive electrodes giving an estimated NO concentration of 400-600 nM; (iii) biochemical assay for NOS using L-arginine/L-citrulline conversion in the CNS which gave a comparable value to that of the rat cerebellum and (iv) specific pharmacological effects of the NO precursor L-arginine and a NOS inhibitor (NG-Nitro-L-arginine) in modulation of chemical connections between NADPH-d-positive and NADPH-d-negative neurones. The very high value of estimated NO concentration and NOS activity and the relatively small number of putative NOS-containing (NADPH-d-positive) cells, including identified sensory (N, P, T cells), motor (AE) and interneurones (151) with known monosynaptic connections, make these neurones an ideal preparation on which to study the possible effects of NO on synaptic interactions.

Animals↗
PubMed1989

Deamination of hordenine by monoamine oxidase and its action on vasa deferentia of the rat.

The selectivity of the naturally occurring amine, N,N-dimethyltyramine (hordenine) for monoamine oxidase (MAO) and its action upon isolated vasa deferentia of the rat was investigated. Hordenine was deaminated by rat liver MAO with a Michaelis constant of 479 microM and maximum velocity of 128 nmol (mg protein)-1 h-1 compared with 144 microM and 482 nmol (mg protein)-1 h-1 for tyramine. Studies, with selective irreversible inhibitors of MAO, showed that hordenine was a highly selective substrate for MAO-B of liver and that it was not deaminated by the MAO-A of intestinal epithelium. In contrast to tyramine, hordenine did not produce contractions of isolated vasa deferentia. However, 25 microM hordenine potentiated contractile responses of vasa, from control animals, to submaximal doses of noradrenaline and inhibited responses to tyramine. It did not alter responses, to noradrenaline, of vasa denervated by chronic pretreatment of rats with guanethidine. Therefore, it appears that hordenine acted as an inhibitor of noradrenaline uptake, in isolated vasa deferentia. These results indicate that dietary-hordenine is unlikely to be deaminated by intestinal MAO as this is predominantly MAO-A. Consequently, it is likely to be absorbed and could affect the sympathetic nervous system, by virtue of its action as an inhibitor of noradrenaline uptake.

Alkaloids↗
PubMed1988

Tonic and rhythmic contractions induced by dopamine and related amines in rat vasa deferentia are pharmacologically separable.

1. Exogenous dopamine (DA), octopamine (OA), noradrenaline (NA), and the alpha 1-agonist methoxamine (MX), all induce tonic and rhythmic contractions in the rat vas deferens. 2. Tonic and rhythmic contractions can be separated by use of different concentrations of alpha 1-adrenoceptor antagonists, verapamil, pyrogallol (a COMT-inhibitor) and lowering bath temperature (greater than 20 degrees C). 3. The two types of contraction could not be distinguished by beta-adrenoceptor antagonists, cocaine (uptake 1 blocker) or metanephrine (uptake 2 blocker). 4. It is suggested that the tonic and rhythmic contractions induced by amines are mediated by different alpha-adrenoceptors.

Amines↗
PubMed1988

Pharmacological control of the pattern of activity in leech Retzius neurones.

1. Changes in the activity pattern of leech Retzius (R) cells were investigated using intracellular recording. 2. The presence of an after-hyperpolarisation (AHP) is closely related to activity pattern; regular firing being associated with an AHP, bursting with its absence. 3. Increasing external calcium (Cao), cyclic AMP levels or activity of kinase A enhanced the AHP. 4. Bursting was induced by low Cao, EGTA, barium, cobalt or injection of phorbol ester. 5. Reduction of Cao to zero caused long paroxysmal depolarising shifts of potential which could be reversed to bursting by cobalt, IBMX or injection of kinase A catalytic subunit. 6. The possible roles of a calcium-activated potassium channel and protein phosphorylation in regulating the activity of the cell are discussed.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Actions of dopamine and related amines on reserpinized and chronically denervated vasa deferentia of the rat.

1. Reserpine, chronic guanethidine denervation and alpha-adrenoceptor antagonists were used to distinguish between presynaptic and postsynaptic actions of exogenous dopamine (DA), octopamine (OA), tyramine (TA) and noradrenaline (NA) on the rat vas deferens. 2. TA has only a presynaptic action while DA and OA have mixed presynaptic actions (releasing endogenous NA) and postsynaptic actions. 3. The postsynaptic actions of DA and OA are likely to be mediated by alpha-adrenoceptors rather than by specific receptors.

Amines↗
PubMed1986

Leech Retzius cells and 5-hydroxytryptamine.

A pair of giant Retzius (R) cells in each segmental ganglion of the leech contain 5-hydroxytryptamine (5-HT). They are the only 5-HT-containing neurones in the central nervous system to send branches to the periphery, yet many peripheral tissues (e.g. body wall muscles, heart, reproductive organs, nephridia and gut) possess 5-HT-like immunoreactive nerve fibres. 5-HT and/or R cell stimulation relax basal tension of body wall muscles and reduce their relaxation times following contraction, enhance pharyngeal movements and salivary gland secretion but inhibit muscle movements of the posterior gut regions and of the reproductive tract. It is suggested that R cells are multifunction neurones modulating activity of many tissues so that feeding behaviour of the leech is carried out as efficiently as possible.

Animals↗
PubMed1985

A new approach to the analysis of complex dose-response relationships: a multivariate study of octopamine action on the leech Leydig neurone.

Octopamine (OA) hyperpolarizes leech Leydig neurones but response amplitudes and thresholds vary. Associations between response, OA dose and other variables [initial resting potential, action potential (AP) frequency and amplitude, temperature, microelectrode resistance, position of ganglion along nerve cord, animal, treatment order] were examined using canonical correlation. A complex response was expressed by summing changes in membrane potential and AP frequency over 2 min of OA treatment. Only dose and ganglion position influenced this response. One significant canonical variate related dose to immediate changes in membrane potential and summed changes in AP frequency throughout the OA effect. Response to OA was greater in cells in posterior ganglia.

Action Potentials↗
PubMed1982

Do pyrethroids activate neurotransmitter receptors?

1. Leech Retzius (R) neurons are excited by carbachol, and this action is blocked by benzoquinonium (Mytolon). 2. Pyrethroids induce spontaneous depolarizations in R neurons. These events are not blocked by benzoquinomium, therefore pyrethroids are not acting on the cholinoreceptor. 3. A congeneric series of synthetic pyrethroids, the QSAR compounds, also induce depolarizations in R cells. The log time to onset of these events is correlated with polarity of the molecule and the structure of the acid moiety, the dichlorovinyl esters being more effective neurotoxicologically than the corresponding chrysanthemates. 4. The depolarizations induced by pyrethroids are not blocked by tetrodotoxin (TTX) in either pressure-sensitive (P) or nociceptive (N) neurons, in which the spike is TTX-sensitive, or in R neurons which have an action potential resistant to TTX. The depolarizations are thus not due to ionic currents moving in through fast sodium channels.

Animals↗