Effects of the partial dopamine receptor agonist, terguride, on the field-stimulated vas deferens in the mouse

Transdihydrolisuride (terguride), a 9,10-dihydrogenated analogue of the ergot dopamine agonist lisuride, is characterized as partial dopamine receptor agonist at CNS level. This compound was investigated for its effects on peripheral neurotransmission in the attempt to delineate its pharmacological profile. The contractile responses of field-stimulated mouse vas deferens were slightly inhibited by terguride at very high concentrations (10(-5)-10(-2) M); the selective antagonists for alpha 2-adrenergic and dopamine receptors failed to counteract this effect. Terguride was very effective in blocking the inhibitory effects of LY 171555 (selective DA2 agonist), SK&F 38393 (selective DA1 agonist) and clonidine (selective alpha 2 agonist). In no case the antagonism was competitive: the control dose-response curves were not shifted in a parallel and dose-dependent manner. Therefore terguride displays a mixed DA1, DA2 and alpha 2 antagonistic activity.     

Effects of neurotropic substances—apomorphine,piribedil, bromocriptine and metergoline—on the excitability of identifiable molluscan giant neurons sensitive to dopamine and 5-hydroxytryptamine

1. It was examined whether four neurotropic substances—apomorphine, piribedil, bromocriptine and metergoline—have either an agonistic or antagonistic effect to dopamine (DA) and 5-hydroxytryptamine (5-HT), by using the two giant neurons (PON, periodically oscillating neuron and TAN, tonically autoactive neuron), which are sensitive to the two putative neurotransmitters and identified in the suboesophageal ganglia of an African giant snail (Achatina fulica Férussac).2. The four neurotropic substances examined at 10⁻⁴ kg/1 had neither an agonistic nor antagonistic effect to both 5-HT and DA on the two giant neurons.3. Both apomorphine and metergoline at 10⁻⁴ kg/1 sometimes produced abnormal spike discharges of TAN, such as the doublet spikes or the slow oscillations of membrane potential.4. Bromocriptine at 10⁻⁴ kg/1 occasionally caused a transient hyperpolarization of the TAN membrane potential, which was probably due to the synaptic influences.     

Novel 8 alpha-ergolines with inhibitory and stimulatory effects on prolactin secretion in rats

Four derivatives of the ergot dopamine (DA) agonist lisuride (LIS), namely 6-n-propyl-lisuride (6-n-propyl-LIS), transdihydrolisuride (TDHL), 6-n-propyl-transdi-hydrolisuride (6-n-propyl-TDHL) and 2-bromolisuride (2-Br-LIS) were investigated in female rats with regard to their influence on hyperprolactinaemia induced by pretreatment with reserpine (2 mg/kg i.p., 24 h) at various intervals following their subcutaneous or oral administration (0.05 mg/kg). Two hours after administration, LIS, 6-n-propyl-LIS, and 6-n-propyl-TDHL caused a statistically significant inhibition of reserpine-induced hyperprolactinaemia of about the same extent. Eight hours after administration 6-n-propyl-LIS and 6-n-propyl-TDHL were as active as after 2 h in inhibiting prolactin (PRL) secretion whereas LIS was almost ineffective in this respect. TDHL caused a statistically significant inhibition of PRL secretion at 2 and 8 h after oral administration; this effect was less pronounced after s.c. administration. In contrast to the aforementioned derivatives 2-Br-LIS further increased the reserpine-induced hyperprolactinaemia. In normal male rats pretreatment with 2-Br-LIS (0.025-6.25 mg/kg s.c., 2 h) dose-dependently stimulated PRL secretion. The present data support the assumption of the longlasting DA agonistic action of 6-n-propyl-LIS and 6-n-propyl-TDHL and of the antidopaminergic properties of 2-Br-LIS recently derived from behavioural studies.     

Characterization of pre- and postsynaptic dopamine receptors in Lymnaea

1. The effects of dopamine and several synthetic agonists and antagonists were studied using two identified neurons of the snail Lymnaea stagnalis. 2. In both the buccal-2 (B-2) neurons and the pedal giant (RPeD1) neuron dopamine elicited a hyperpolarizing response at least partly due to potassium efflux. RPeD1 is itself dopaminergic, implicating autoreceptors in its response to dopamine. 3. The following agents were tested: agonists--LY171555, pergolide, SKF38393, (-)-3-PPP, R(-)NPA and dopamine; antagonists--SCH23390, sulpiride, and metaclopramide. Dibutyryl cAMP was applied to determine whether the response is cAMP-mediated. 4. Results indicate that the pharmacological profiles of dopamine receptors on these neurons are inconsistent with those of either D-1, D-2 or autoreceptors in mammals.     

Pharmacological characteristics of three silent giant neurons, v-LPSN, v-1-VOrN and v-VLN, identified on the ventral surface in the left parietal and the visceral ganglia of the suboesophageal ganglia of an African giant snail (Achatina fulica Férussac)

Three giant neurons, named v-LPSN, v-1-VOrN and v-VLN, were identified on the ventral surface of the left parietal ganglion and the visceral ganglion in the suboesophageal ganglia of an African giant snail (Achatina fulica Férussac). They lacked the spontaneous spike discharges in the normal state. The pharmacological features of the three neurons, in relation to the principal common neurotransmitter substances and their derivatives were examined. The v-LPSN (ventral-left parietal silent neuron) (diameter: about 130 microns) is situated in the left parietal ganglion close to the visceral ganglion. The neuron was excited by histamine (the minimum effective concentration [MEC]: 3 X 10(-4) M) and inhibited slightly by acetylcholine (Ach) and its related substances. The v-1-VOrN (ventral-left-visceral oral neuron) (diameter: about 130 microns) is situated in the left and oral part of the visceral ganglion. The neuron was inhibited markedly by dopamine (DA) (MEC: 3 X 10(-4) M) and slightly by Ach and its related substances. No substance producing a marked excitation of the neuron has been found yet. The v-VLN (ventral-visceral large neuron) (diameter: about 300 microns) is found in the centre of the visceral ganglion. The neuron was excited by L-norepinephrine (MEC: 10(-4) M), DL-octopamine (MEC: 2 X 10(-4) M), 5-hydroxytryptamine (MEC: 10(-4) M) and beta-hydroxy-L-glutamic acid (MEC: 10(-4) M) and inhibited by DA (MEC: 10(-4) M), GABA (MEC: 3 X 10(-5) M) and Ach (MEC: 10(-4) M). L-Epinephrine showed varied effects (MEC: 10(-4) M), which were either excitatory or inhibitory.     

Central antidopaminergic properties of 2-bromolisuride, an analogue of the ergot dopamine agonist lisuride

2-Bromolisuride (2-Br-LIS), a derivative of the ergot dopamine (DA) agonist lisuride, was investigated in rodents in comparison with the DA antagonist haloperidol with regard to its influence on DA related behaviour, cerebral DA metabolism and prolactin (PRL) secretion. 2-Br-LIS produced catalepsy in mice (ED50 3.3 mg/kg i.p.), antagonized apomorphine-induced stereotypies in mice (ED50 0.4 mg/kg i.p.), antagonized DA agonist-induced stereotypies in rats (0.1-1.56 mg/kg i.p.), inhibited locomotor activity in rats (0.025-6.25 mg/kg i.p.), antagonized the hyperactivity produced by various DA agonists in rats (0.025-6.25 mg/kg i.p.) and inhibited the apomorphine-induced hypothermia in mice (0.05-0.78 mg/kg i.p.). 2-Br-LIS (0.03-10 mg/kg i.p.) stimulated DA biosynthesis and DOPAC formation in the striatum and DA rich limbic system of rats, but had no effect on serotonin turnover. In striatum and limbic forebrain of gamma-butyrolactone-pretreated rats 2-Br-LIS reversed the apomorphine-induced inhibition of DOPA accumulation. 2-Br-LIS (0.03 - 3 mg/kg) enhanced PRL secretion in intact male rats. These findings indicate DA antagonistic properties of 2-Br-LIS presumably due to blockade of central pre- and postsynaptic DA receptors being of approximately the same order of potency as haloperidol. 2-Br-LIS is the first ergot compound with definite antidopaminergic properties suggesting its potential usefulness as a neuroleptic.     

Isolation of achatin-I, a neuroactive tetrapeptide having a D-phenylalanine residue, from Achatina ganglia, and its effects on Achatina giant neurones.

1. We have isolated a neuroexcitatory tetrapeptide having a D-phenylalanine (Gly-D-Phe-L-Ala-L-Asp) from the ganglia of Achatina fulica Férussac. This peptide was termed achatin-I (Kamatani et al., 1989). In the present report, we shall present highlights from the original paper concerning the process of peptide isolation and the examination of its effects. 2. From the ganglia of about 30,000 animals, we obtained 50 micrograms of achatin-I and 17 micrograms of its stereoisomer consisting of only L-amino acid residues (Gly-L-Phe-L-Ala-L-Asp) which was termed achatin-II. The data of instrumental analyses (1H-NMR, SIMS, CD and HPLC) of isolated achatin-I and achatin-II were identical to those of synthetic ones. 3. Achatin-I showed marked excitatory effects on the three Achatina giant neurones, PON (periodically oscillating neurone), TAN (tonically autoactive neurone) and v-RCDN (ventral-right cerebral distinct neurone), whereas achatin-II had no effect. Among their stereoisomers, [D-Ala3]-achatin-I (Gly-D-Phe-D-Ala-L-Asp) had slight excitatory effects on the Achatina neurones tested. Amide derivatives of achatin-I and achatin-II were ineffective. 4. Dose-response curves of achatin-I and [D-Ala3]-achatin-I for producing the inward current of PON were measured under voltage clamp at a holding membrane voltage (Vh) of -50 mV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Classification of the responses of a giant neuron from the snail Acatina fulica Férussac, caused by inhibitory sugstances depending on chlorine ions]

GABA, three of its derivatives (l-GABOB, d-GABOB and delta-amino valeric acid), acetycholine (Ach), dopamine (DA) and l-Phe-Tyr all inhibit an identifiable giant neurone (the TAN, tonically autoactive neurone) of Achatina fulica. These effects were examined by microdrop application in two different conditions: in physiological solution and in the absence of chloride ions. The results show that the relatively transient (rapid) inhibitions caused by GABA, by its derivatives and by Ach are dependent on chloride ions; the relatively maintained (long-lasting) inhibitions, caused by DA and l-Phe-Tyr, are independent of chloride ions.     

Identification and pharmacological characteristics of the two giant neurons, v-RPLN and v-VNAN, on the ventral surface in the suboesophageal ganglia of the African giant snail (Achatina fulica Férussac)

Two giant neurons, v- RPLN (ventral-right parietal large neuron) and v- VNAN (ventral-visceral noisy autoactive neuron), were identified on the ventral surface in the caudal part of the suboesophageal ganglia of the African giant snail (Achatina fulica F erussac ), and their pharmacological features to the common putative neurotransmitters and their related substances were examined. The giant neuron examined, v- RPLN , is situated in front of the exit of the right anterior pallial nerve in the right parietal ganglion. The neuron, which is 250-300 microns in diameter, one of the largest neurons in the ganglia, was usually silent without spontaneous firing. The neuron was excited by L-norepinephrine (L-NE), DL-octopamine (DL-OA), 5-hydroxytryptamine (5-HT), L-homocysteic acid (L-HCA) and erythro-beta-hydroxy-L-glutamic acid (erythro-L- BHGA ); and inhibited by dopamine (DA), GABA, acetylcholine (Ach) and its related substances. Another giant neuron examined, v- VNAN , is situated very close to the right side of the exit of the right posterior pallial nerve in the visceral ganglion. The neuron is elliptical and about 150 micron in diameter. It showed spontaneous firing highly modified by the synaptic influences. DA, 5-HT, glycine (Gly), GABA and its related substances, L-HCA, erythro-L- BHGA , and Ach and its related substances all had the direct (not via synaptic influences) excitatory effects on the neuromembrane examined. Some of them, for example, L-NE, 5-HT and Ach and its related substances caused transient excitation of the neuron, probably due to the synaptic influences, immediately after their application. No substance producing any inhibition of the neuron could be found in the present study.     

Further study of effects of synthetic peptides on identifiable giant neurones of an African giant snail (Achatina fulica Férussac)

1. Effects of the following peptides at 10(-4) M on identifiable giant neurones of Achatina fulica Férussac were examined: physalaemin, eledoisin, bradykinin, neurokinin A, neurokinin B, neuromedin B, gastrin releasing peptide decapeptide (neuromedin C), gastrin releasing peptide (14-27), cholecystokinin tetrapeptide, cholecystokinin octapeptide, thyrotropin releasing hormone, Arg-vasotocin, gamma-melanocyte stimulating hormone. 2. The six neurones tested were as follows: PON (periodically oscillating neurone), TAN (tonically autoactive neurone), RAPN (right anterior pallial neurone), d-RPLN (dorsal-right parietal large neurone), VIN (visceral intermittently firing neurone) and d-VLN (dorsal-visceral large neurone). 3. Of the peptides examined, only Arg-vasotocin at 10(-4) M produced the excitatory effects on PON, VIN and d-VLN. Physalaemin showed slight inhibitory effects on TAN; this substance was sometimes almost ineffective on the neurone. 4. The other peptides examined were completely ineffective on all of the neurones tested.     

Specific Involvement of Central 5-HT1A Receptors in the Mediation of Male Rat Ejaculatory Behavior

The aminotetralin 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), pharmacologically characterized as a 5-HT_1A receptor agonist, produces a pronounced decrease in ejaculation latency in the male rat. Stimulation of 5-HT receptors by a pharmacologically induced increase in the synaptic availability of 5-HT has been shown to produce the opposite effect. The 8-OH-DPAT-induced decrease in ejaculation latency is specific for this compound, and some chemically related ergot derivatives. In this paper we review the evidence in support for stimulation of serotonergic auto-receptors of the 5-HT_1A receptor subtype as a mechanism of action for effects by 8-OH-DPAT on male rat ejaculatory behavior. We also present the questions posed by the fact that quinpirole and lisuride both produce 8-OH-DPAT-like effects on male rat ejaculatory behavior. The effects by quinpirole, lisuride or 8-OH-DPAT are not sensitive to pretreatment with the DA D_2/3 receptor antagonist raclopride. Continued studies will show whether the effects of quinpirole and lisuride can be related to stimulation of 5-HT_1A receptors, or if all these compounds have as yet undefined common properties.     

Striatal cholinergic function reflects differences in D-2 dopaminergic receptor activation

The ergot derivatives, bromocriptine, lisuride and quinpirole (Ly-171555), activators of D-2 receptors, increased striatal acetylcholine (ACh) content by about 40% and induced a 30% inhibition of ACh evoked release from striatal slices, similar to the effects of the dopaminergic agonist apomorphine. These actions were a consequence of dopaminergic activation since they were antagonized by pretreatment with the neuroleptic agent, pimozide. In contrast, pretreatment with L-sulpiride (100 mg/kg), a specific antagonist for the D-2 dopaminergic receptor only, prevented the rise of ACh levels induced by apomorphine or quinpirole but did not interfere with the lisuride- or bromocriptine- induced ACh increases. Similarly, inhibition of the ACh evoked release produced by lisuride (3ωM) was prevented by pimozide (1mg/kg) but not by pretreatment with L-sulpiride. Addition of L-sulpiride (5ωM) to the Krebs solution had no effect on the inhibition of ACh-evoked release induced by lisuride, but a lower concentration (1ωM) antagonized the inhibition induced by quinpirole. Lisuride and bromocriptine responses were both insensitive to sulpiride. These results are discussed in terms of different interaction with the dopaminergic D-2 receptors by the drugs studied.     

Hyperactivity induced by stimulation of separate dopamine D-1 and D-2 receptors in rats with bilateral 6-OHDA lesions

The effects of DA agonists and antagonists with different dopamine (DA) D-1 and D-2 receptor selectivity have been studied in rats with bilateral 6-OHDA lesions. The D-1 agonist SK & F 38393, the D-2 agonist pergolide and the mixed agonist apomorphine all induced marked hyperactivity in lesioned rats in doses which were without stimulant effect in sham-operated animals. The hyperactivity induced by SK & F 38393 was blocked by the DA D-1 antagonist SCH 23390, but unaffected by the D-2 antagonists spiroperidol or clebopride. Pergolide-induced hyperactivity showed the reverse selectivity. The mixed D-1/D-2 antagonists, cis(Z)-flupentixol and cis(Z)-clopenthixol, however blocked the effect of both agonists. Apomorphine-induced hyperactivity was neither blocked by selective D-1 nor D-2 antagonists, but was dose-dependently inhibited by cis(Z)-flupentixol and cis(Z)-clopenthixol. Potent blockade was also obtained by combined treatment with SCH 23390 and spiroperidol, indicating the need of blocking both D-1 and D-2 receptors simultaneously. The results indicate that D-1 and D-2 receptor function can be independently manipulated in denervated rats and they confirm similar results obtained in rats with unilateral 6-OHDA lesions using circling behaviour.     

Automated high-performance liquid chromatographic method for the analysis of two novel ergoline compounds in human plasma

A rapid and sensitive high-performance liquid chromatographic method for the determination of the novel ergoline derivatives sergolexole (compound I), its acid metabolite (compound II) and cis-n-(2-hydroxycyclopentyl)-6-methyl-1-(1-methylethyl) ergoline-8-carboxamide (LY215840, compound III) in human plasma is reported. The compounds were extracted from plasma by automated solid-phase extraction and analysed on a reversed-phase C₈ column with fluorescence detection. The limit of quantification for all compounds was 10 ng/ml and the response was linear over the range 10–1000 ng/ml. Validation studies showed the method to be both repeatable and reproducible with no interference from human plasma. The method has been used to support pharmacokinetic studies and has proved to be robust and effective.     

The effect of mesulergine on prolactin secretion and anterior pituitary cells morphology in diethylstilboestrol-treated female Wistar rats.

Mesulergine (Cu32-085) is an active semisynthetic ergot alkaloid with unusual biphasic antagonistic-agonistic effect on dopamine (DA) turnover in the rat striatum. The present study has been made to elucidate the influence of the long-term treatment of this drug on prolactin secretion and prolactin cells morphology in the female Wistar rats with experimentally-induced hyperprolactinemia. Additionally, the effect of this drug was compared with bromocriptine and pergolide activity, applied in the same experimental conditions. It has been shown that prolonged mesulergine treatment attenuated the stimulatory effect of stilboestrol on prolactin secretion in vivo. It also decreased mean prolactin cells density, above all cells and lactotroph mitotic indexes, estimated in immunohistochemically-stained slides. However, antiproliferative activity of Cu 32-085 was weaker, when compared with bromocriptine and pergolide.     

Decreases of action potential amplitudes, in sodium-free and calcium-free conditions, of identifiable giant neurons of an African giant snail (Achatina fulica Férussac)--I. The right parietal ganglion

Decreases of the action potential amplitude in sodium- and calcium-free states were observed with respect to the four giant neurons, PON (periodically oscillating neuron), Tan (tonically autoactive neuron), RAPN (right anterior pallial neuron) and d-RPLN (dorsal-right parietal large neuron), identified in the right parietal ganglion of the suboesophageal ganglia of an African giant snail (Achatina fulica Férussac). The decrease of the PON action potential amplitude, caused in the sodium-free state, was observed to be 25.4 +/- 2.1% (23.0 +/- 2.0 mV), expressed by M +/- SE, while that of the calcium-free state was 35.0 +/- 2.1% (30.9 +/- 1.7 mV). Then, the two ionic dependencies of the PON action potential were estimated to be about 40-50% on sodium and 50-60% on calcium. The decrease of the TAN action potential in the sodium-free state, was observed to be 20.7 +/- 1.2% (18.8 +/- 1.3 mV), whereas that of the calcium-free state was 42.2 +/- 2.7% (39.0 +/- 2.2 mV), indicating that the two ionic dependencies were 30-40% on sodium and 60-70% on calcium. The decrease of the RAPN action potential in the sodium-free state, was 45.8 +/- 3.7% (40.3 +/- 3.1 mV), whereas that of the calcium-free state was 21.7 +/- 2.5% (17.8 +/- 2.0 mV), indicating that the two ionic dependencies were about 70% on sodium and about 30% on calcium. The decrease of the d-RPLN action potential in the sodium-free state was found to be 17.6 +/- 2.4% (15.2 +/- 1.8 mV), whereas that of the calcium-free state was 23.1 +/- 1.4% (20.8 +/- 1.4 mV), indicating that the two ionic dependencies were 40-50% on sodium and 50-60% on calcium. The action potential amplitudes of all the neurons tested were decreased in both sodium-free and calcium-free states. However, their ionic dependencies were estimated to vary from 70% on sodium (30% on calcium) to 30% on the sodium (70% on the calcium), according to the neurons tested.     

Structure-activity relationship studies on the endogenous neuroactive tetrapeptide achatin-I on giant neurons of Achatina fulica Ferussac.

The structure-activity relationships of achatin-I, a neuroactive peptide containing a D-phenylalanine residue, for producing excitatory effects on three different types of Achatina neurons, PON, TAN and d-RCDN, were studied under the voltage clamp method. Of the peptides examined, only Gly-Gly-D-Phe-L-Ala-L-Asp (IV). D-Phe-L-Ala-L-Asp (V) and Gly-D-Phe-L-Ala-L-Asn (XVI) produced an inward current with increased membrane conductance similar to achatin-1 (I). The structure-activity relationship was essentially the same for the three Achatina neuron types. The equiactive molar ratios (EMRs) of the active peptides vs. achatin-I (I) were calculated from their dose-response curves: 8 - 60 for Gly-Gly-DPhe-L-Ala-L-Asp (IV), 200 - greater than 250 for D-Phe-L-Ala-L-Asp (V) and greater than 200 for Gly-D-Phe-L-Ala-L-Asn (XVI). These values indicate that the achatin-I receptor in the Achatina neurons is highly structure-specific.     

Pharmacological characteristics of the two largest neurons symmetrically situated in the suboesophageal ganglia of an African giant snail (Achatina fulica férussac)

1. Pharmacological characteristics of the two largest neurons, r-PLN (right-parietal large neuron) and d-VLN (dorsal-visceral large neuron), situated symmetrically on the anterior-dorsal surface in the suboesophageal ganglia of an African giant snail (Achatina fulica Férussac), were determined.2. Of the catecholamines examined, dopamine (DA) showed marked but complex effects on the two neurons. DA produced a transient excitation followed by either hyperpolarization or depolarization of the neuromembranes. L-Norepinephrine produced a slight depolarization of the neurons.3. 5-Hydroxytryptamine (5-HT) produced marked excitation of both neurons. Bufotenine showed the same effects, but they were weaker than those of 5-HT.4. Histamine showed inhibatory effects on the two neurons examined, whereas L-histidine had rather slight or no excitatory effects.5. Of the amino acids examined, L-homocysteic acid (L-HCA) and erythro-β-hydroxy-L-glutamic acid had marked excitatory effects on r-PLN and d-VLN. L-Homocysteine sulfinic acid also showed the excitatory effects, but they were weaker than those of L-HCA. Glycine and L-methionine had slight excitatory effects on both neurons, whereas L-aspartic acid, L-glutamic acid and GABA had none.6. Acetylcholine (ACh) exhibited marked and complex effects on r-PLN and d-VLN. In trials, ACh produced either excitation or inhibation of both neurons. Propionylcholine and butyrycholine had slightly less effect, producing a slight inhibation of r-PLN and either excitation or inhibation of d-VLN in trials.     

Influence of imidazole on behavioral effects induced by dopaminergic agonists in rats

Imidazole (IMI) (from 18.7 to 300 mg/Kg) i.p. injected in adult rats induced shaking, which was antagonized by both morphine (MOR) and haloperidol (HALO) but not by methysergide (MET). I.p. IMI pretreatment inhibited the penile erections (PE) and stretching and yawning (SY) typically elicited by N-n-propylnorapomorphine (NPA), a well-known CNS dopamine (DA) receptor stimulant, injected either i.p. or i.c.v., whereas it enhanced stereotyped behavior (SB). IMI had similar effects on the same parameters considered when injected before lisuride, an ergot derivative also active as a central DA receptor agonist. In this case not only SB but also and above all aggressiveness were markedly potentiated, both the signs appearing at doses of lisuride which were "per se" ineffective. Aggressiveness, like SB, was not sex linked and was antagonized by HALO and MOR, but not by MET. IMI alone potentiated the fighting induced by electrical shock, an effect which was abolished by HALO pretreatment. Considering the results obtained as a whole it is submitted that IMI antagonizes PE and SY through a selective blockade of a class of DA receptors, presumably DA presynaptic autoinhibitors, thus potentiating SB and aggressiveness, which involve stimulation of DA postsynaptic receptors.     

Effect of oligopeptides containing L-Phe, L-Tyr, L-Trp, L-His or L-Met on the excitability of the 2 giant neurons of the African giant snail (Achatina fulica Ferussac)]

Effects of about ninety oligopeptides, containing L-Phe, L-Tyr, L-Trp, L-His and L-Met, on the excitability of two identifiable giant neurones (the PON, periodically oscillating neurone ; and the TAN, tonically autoactive neurone) of Achatine fulica Férussac were examined. Three oligopeptides, L-Lys-L-Phe-L-Tyr, L-Phe-L-Tyr and L-Phe-L-Trp, showed an inhibitory effect on the PON. However, this effect on the PON was weaker than that of the same three peptides on the TAN. [The latter has been reported in previous papers (1 to 3)]. Besides the three oligopeptides mentioned, four peptides, L-Phe-L-Phe, L-Phe-L-Phe-L-Phe, L-Tyr-L-Tyr and L-Tyr-L-Tyr-LTyr, still showed a weak inhibitory effect on the TAN in a high concentration.