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PubMed1991

Organic Ca(2+)-antagonist-resistant response to FMRF-NH2 on the molluscan smooth muscle.

1. FMRF-amide (10(-7)-10(-5) M) contracted molluscan anterior byssus retractor muscle in a concentration-dependent fashion. 2. The concentration-response curve of FMRF-amide was shifted rightward by an analogue of FMRF-amide, FMRf-amide ([D-Phe4]FMRF-amide, putative FMRF-amide receptor antagonist) in a parallel manner (pA2 = 4.87 +/- 0.04). 3. Although a contractile response to KCl was reduced by the organic Ca2+ antagonists (verapamil, diltiazem and high concentration of nifedipine and nicardipine). FMRF-amide-induced contraction was not markedly reduced by them. 4. In the Ca(2+)-free medium, FMRF-amide-induced contraction was diminished. The response was also reduced by TMB-8 (10(-4) M), suggesting that FMRF-amide-induced contraction might be partly dependent on intracellular Ca2+. 5. An inorganic Ca(2+)-antagonist, MnCl2, markedly reduced the FMRF-amide- and KCl-induced contraction. The results show that FMRF-amide-induced contraction might be dependent on extracellular Ca2+. 6. These findings suggest that FMRF-amide-induced contraction might be mediated through an action on FMRF-amide receptors and not through the activation of organic Ca2+ antagonist-sensitive Ca2+ channels.

Animals↗
PubMed1984

The immunohistochemical localization of nine peptides in the sacral parasympathetic nucleus and the dorsal gray commissure in rat spinal cord.

The sixth lumbar and first sacral spinal cord segments in the rat contain parasympathetic preganglionic neurons which innervate the pelvic viscera. There have been few studies, however, which have specifically considered the distribution of putative peptide neurotransmitters in these cord segments. The present paper describes and compares the immunohistochemical distribution of dynorphin (1-8)-, enkephalin-, somatostatin-, cholecystokinin octapeptide-, avian pancreatic polypeptide-, FMRF-NH2-, neurotensin-, and vasoactive intestinal polypeptide-like immunoreactivities in the dorsal gray commissure and sacral parasympathetic nucleus of the sixth lumbar and first sacral spinal cord segments in colchicine-treated rats. Antisera against all of the peptides, except avian pancreatic polypeptide, stained cells in the sacral parasympathetic nucleus. Dynorphin (1-8-), enkephalin-, and substance P-like immunoreactive cells were present in significantly greater numbers than somatostatin-, neurotensin-, cholecystokinin-, FMRF-NH2-, and vasoactive intestinal polypeptide-like immunoreactive cells. All of the antisera also stained fibers in the sacral parasympathetic nucleus in varying densities, and a fiber bundle which extended between the dorsal gray commissure and the sacral parasympathetic nucleus. Antisera against substance P and cholecystokinin stained a bundle of fibers that extended between the dorsal horn and the sacral parasympathetic nucleus. Antisera against somatostatin, cholecystokinin octapeptide, substance P and FMRF-NH2 stained an additional fiber bundle which extended between the lateral edge of the dorsal horn and the dorsal gray commissure. All the remaining antisera, except neurotensin, also stained fibers that extended between the sacral parasympathetic nucleus and the dorsal gray commissure, but in a sparser distribution. Immunoreactive cells were localized to the dorsal gray commissure in sections stained with each of the antisera. Dynorphin (1-8) and enkephalin antisera stained the greatest number of cells, followed by FMRF-NH2, neurotensin, somatostatin and avian pancreatic polypeptide. The smallest number of immunoreactive cells was present in substance P, cholecystokinin and vasoactive intestinal polypeptide immunostained sections. A significant difference was noted between the number of dynorphin, enkephalin, somatostatin, cholecystokinin, avian pancreatic polypeptide, FMRF-NH2, neurotensin and vasoactive intestinal polypeptide immunoreactive cells in the sacral parasympathetic nucleus and dorsal gray commissure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Involvement of Ca2+ uptake by a reticulum-like store in the control of transmitter release.

At an identified neuro-neuronal synapse of Aplysia, 2,5-diterbutyl 1,4-benzohydroquinone, a selective blocker of the reticulum Ca2+ pump, was found to potentiate evoked quantal release of acetylcholine through an increased accumulation of Ca2+ in the presynaptic neuron during depolarization without any accompanying changes in the presynaptic Ca2+ current. We conclude that a rapid Ca2+ buffering system, similar to that associated with the endoplasmic reticulum, must be present in the nerve terminal and play a role in the control of Ca2+ which reaches the release system.

Animals↗
PubMed1984

Distribution of FMRF-NH2-like immunoreactivity in rat and cat area postrema.

The distribution of FMRF-NH2-like immunoreactivity, visualized with immunohistochemical techniques, was plotted in a range from very dense to none. The rat area postrema had differential immunostaining with the greatest amounts occurring at its ventral and ventrolateral borders by the nucleus of the solitary tract. Immunoreactive cell bodies were located mainly in this region. Throughout the central region of the rat area postrema scattered immunostaining was consistently observed. The cat area postrema had a different, greater, and more complex pattern of immunostaining than the rat. Very dense to dense accumulations of immunostaining occurred in the ventromedial region of the area postrema bordering the solitary tract and dorsal vagal nuclei, while the central region possessed scattered amounts of immunoreactivity. Following colchicine treatment, no visible FMRF-NH2-like immunoreactive cell bodies were observed in the cat area postrema.

Animals↗
PubMed1985

Actions of the molluscan neuropeptide FMRF-amide on neurones in the suboesophageal ganglia of the snail Helix aspersa.

The effects of the molluscan neuropeptide FMRF-amide were tested on several neurones in the suboesophageal ganglia of the snail Helix aspersa. Almost all neurones tested responded to the peptide, some being hyperpolarized (H response) and others depolarized (D response). The H response is due primarily to an inward potassium current and may be blocked in 20 microM 4-aminopyridine. The hyperpolarizing actions of FMRF-amide and dopamine may be separated by ergometrine which blocks the response to dopamine but not to FMRF-amide. The D response is due mainly to an inward sodium current but this is not blocked by d-tubocurarine, morphine or TTX. It appears to be mediated by a distinct receptor/ionophore as excitation by ACh and 5-HT are both antagonized by d-tubocurarine. The Leu2-substituted analogue FLRF-amide was found to produce similar H responses to FMRF-amide, but was much less potent at producing D responses. It did, however, produce cross-desensitization of the D response to FMRF-amide, suggesting that it does bind to the FMRF-amide receptor.

Animals↗
PubMed1987

Comparison of the effects of FMRF-amide and pQDPFLRF-amide on identified Helix neurons.

Intracellular recordings were made from a selection of identified neurons in the sub-oesophageal ganglia of Helix aspersa, and their responses to the molluscan neuropeptides FMRF-amide and pQDPFLRF-amide compared. While FMRF-amide excited certain neurons and inhibited others, pQDPFLRF-amide did not produce excitation in any of the cells tested. A few cells were unresponsive to pQDPFLRF-amide, but most were inhibited with varying potency. FMRF-amide was generally 10-100 times more potent than pQDPFLRF-amide, but one cell, E13 in the visceral ganglion, showed equal sensitivity to the two peptides. On most cells there was no clear evidence for cross desensitization between the two peptides, although it is possible that in some cases where both peptides are inhibitory they may be acting on a single receptor.

Action Potentials↗
PubMed1993

Roles for arachidonic acid and GTP-binding proteins in synaptic transmission.

Using synapses which form between somata of Helisoma neurons in cell culture we have studied the presynaptic regulation of synaptic transmission. GTP-binding proteins play important roles in regulating synaptic transmission through their actions on calcium currents, potassium currents and secretory apparatus. Heterotrimeric G proteins continuously regulate the amount of transmitter released at the synapse. By interacting with the arachidonic acid second messenger system they modulate potassium channels, and could potentially control the secretory apparatus. Perturbations of the rab protein system did not affect action potential-evoked transmission, but did control the frequency of miniature inhibitory postsynaptic currents. This is consistent with the involvement of this type of GTP-binding protein in the control of secretory apparatus, but suggests that rab proteins are not used to regulate the amount of transmitter released at the synapse. Using the Helisoma cellular system which permits direct access to the presynaptic site of transmitter release we are going on to study further the role of arachidonic acid, Go, Gi and rab proteins on the regulation of the secretory apparatus.

Amino Acid Sequence↗
PubMed2004

Presumptive FMRF-amide-like immunoreactive retinopetal fibres in Crocodylus niloticus.

A small contingent of 30-50 of centrifugal visual fibres, showing FMRF-amide-like immunoreactivity, has been identified in C. niloticus; these fibres extend from the chiasmatic region into the retina. They do not take the marginal optic tract, but pass medially to the chiasmatic fascicles, from the preoptic region. The cells of origin of these fibres have not been identified. However, none of the retinopetal neurons of the brainstem [M. Medina, J. Reperant, R. Ward, D. Miceli, Centrifugal visual system of Crocodylus niloticus : a hodological, histochemical and immunocytochemical study, J. Comp. Neurol. 468 (2004) 65-85], labelled by retrograde transport of rhodamine beta-isothiocyanate after intraocular injection of this tracer, show FMRF-amide-like immunoreactivity; neither are any of the FMRF-amide-like immunopositive neurons in the crocodile brain, particularly those of the complex involving the terminal nerve and the septo-preoptic region, labelled by rhodamine after its intraocular injection.

Alligators and Crocodiles↗
PubMed2005

GnRH-immunoreactive centrifugal visual fibers in the Nile crocodile (Crocodylus niloticus).

Thin varicose centrifugal visual fibers, between 30-45 in number and displaying cGnRH-I immunoreactivity, were identified in Crocodylus niloticus. Approximately 80% of these fibers were also FMRF-amide-like immunoreactive. The cGnRH-I fibers extended from the preoptic region to the retina where they appeared to terminate in the external portion of the inner plexiform layer. The location of their neurons of origin could not be determined precisely following the intraocular injection of the retrograde axonal tracer RITC. Nevertheless, the presence of cGnRH-I-immunoreactive neurons exclusively within the complex comprising the terminal nerve and the septo-preoptic region, and of several retinopetal fibers labelled retrogradely with the axonal tracer at the septo-preoptic junction, indicates that the cGnRH-immunoreactive centrifugal visual system originates from within this complex.

Alligators and Crocodiles↗
PubMed2005

RFamide neuropeptide actions on the molluscan ventricle: Interactions with primary neurotransmitters.

Different RFamide neuropeptides, some of non-molluscan origin, were examined for their effect on the ventricles of Buccinum undatum and Busycon canaliculatum. None of the peptides tested were inhibitory on these ventricles. All the peptides were extremely active, causing excitation of the preparations at low concentrations. The neuropeptides were then tested with the primary neurotransmitters. In the case of serotonin, the excitatory primary neurotransmitter, the RFamide neuropeptides induced a response, which was greatly enhanced by serotonin. Acetylcholine, the inhibitory neurotransmitter, induced relaxation whenever added, following a neuropeptide. The neuropeptides seemed to be independent of external Ca(2+), since in Ca(2+)-free media tension was induced. On the contrary, serotonin was dependent on external Ca(2+). These findings indicate that the neuropeptides generated tension via a different receptor to that of the primary neurotransmitters, using a different 2nd messenger and activating different Ca(2+) sources. Finally, the parent neuropeptide Phe-Leu-Arg-Phe-NH(2), when added following a different RFamide peptide, excited the preparation further, thus indicating the presence of a receptor that has higher affinity for some structures than others. When Phe-Met-Arg-Phe-NH(2) followed Phe-Leu-Arg-Phe-NH(2), no such response was recorded since the latter is of higher potency than the former.

Acetylcholine↗
PubMed2005

The 5-HT- and FMRFa-activated signaling pathways interact at the level of the Erk MAPK cascade: potential inhibitory constraints on memory formation.

The sensorimotor synapse of Aplysia exhibits long-term facilitation (LTF) and long-term depression (LTD) elicited by the neuromodulator serotonin (5-HT) and the peptide Phe-Met-Arg-Phe-NH(2), respectively. 5-HT-induced LTF engages extracellular-regulated kinase (Erk) and CREB1, whereas FMRFa-induced LTD engages p38 MAPK (mitogen-activated protein kinase) and CREB2. The interaction of the 5-HT and FMRFa pathways was recently investigated in Aplysia at the level of gene expression. However, little is known about crosstalk of these pathways at the level of the second messenger cascades. We investigated the potential interaction of the 5-HT and FMRFa pathways at the level of the Erk cascade. We found that FMRFa inhibited basal Erk activity through p38 MAPK. FMRFa also inhibited 5-HT-induced phosphorylation of Erk and nuclear accumulation of phospho-ERK, suggesting that FMRFa may place inhibitory constraints on memory formation through regulation of the Erk MAPK cascade.

Animals↗
PubMed2006

Sensitivity of pressor responses to central hypertonic saline is greatly enhanced even in pre-hypertensive spontaneously hypertensive rats.

It has been suggested that intracerebroventricular injection of hypertonic saline mimics the effects of a high salt diet in spontaneously hypertensive rats (SHR), a genetic model of hypertension. Intracerebroventricular injection of hypertonic saline produces an increase in blood pressure and the pressor response to hypertonic saline is enhanced in adult hypertensive SHR. In this study, we examined whether the intracerebroventricular hypertonic saline-induced pressor response is enhanced even in pre-hypertensive SHR. The basal mean blood pressure was almost the same in 4-week-old SHR and age-matched Wistar Kyoto rats (WKY), whereas it was greater in 15-16-week-old SHR than in age-matched WKY. Intracerebroventricular injection of hypertonic saline (10 microl of 230 mM NaCl) produced an increase in blood pressure in both 4-week-old and 15-16-week-old SHR, whereas it did not affect blood pressure in both age-matched WKY. Intracerebroventricular injection of hypertonic saline (10 microl of 260 mM NaCl) produced an increase in blood pressure in all rats but the pressor response was greater in both 4-week-old and 15-16-week-old SHR than in respective age-matched WKY. Intracerebroventricular injection of Phe-Met-Arg-Phe amide (FMRF), an FMRF-inducible sodium channel activator, produced an increase in blood pressure in all rats but the pressor response was greater in SHR than in WKY at both ages. These findings indicate that the sensitivities of pressor responses to intracerebroventricular hypertonic saline and FMRF are enhanced not only in hypertensive but also in pre-hypertensive SHR.

Animals↗
PubMed2006

Chimeric peptide of met-enkephalin and FMRFa: effect of chlorination on conformation and analgesia.

In our previous study YFa (YGGFMKKKFMRFa), a chimeric peptide of met-enkephalin and FMRFa, not only produced analgesia but also did not let the tolerance develop. In the continuation of the same study, Phe4 is chlorinated so as to assess the effect of chlorination on the conformation, lipophilicity and analgesia of chimeric peptide [p-Cl Phe(4)] YFa. Not only does the chlorination increase the lipophilicity but also enhances the propensity of [p-Cl Phe(4)] YFa to form alpha helix in comparison of YFa in presence of membrane mimicking solvent trifluoroethanol (TFE). This increase in lipophilicity and helix-forming ability results in more bioavailability and naloxone-reversible analgesia by [p-Cl Phe(4)] YFa. Though analgesia produced by [p-Cl Phe(4)] YFa is more than YFa at all doses, there is sudden decrease in analgesia at 45 and 60 min at 60 mg/kg. This sudden decrease of analgesia seems to be due to desensitization of opioid receptors.

Analgesia↗
PubMed2005

Peptidergic neuromodulation of the lumbar locomotor network in the neonatal rat spinal cord.

It is now well established that a dynamic balance of neurotransmitters and neuromodulators finely influence the output of neuronal networks and subsequent behaviors. In the present study, to further understand the modulatory processes that control locomotor behavior, we investigated the action of 11 neuropeptides, chosen among the various peptide subfamilies, on the lumbar neuronal network in the in vitro neonatal rat spinal cord preparation. Peptides were bath-applied alone, in combination with N-methyl-D,L-aspartate (NMA) or with the classical 'locomotor cocktail' of NMA and serotonin. Using these different experimental paradigms, we show that each peptide can neuromodulate the lumbar locomotor network and that peptides exhibit different neuromodulatory profiles and potencies even within the same family. Only vasopressin, oxytocin, bombesin and thyrotropin releasing hormone triggered tonic or non-organized rhythmic activities when bath-applied alone. All the neuropeptides modulated NMA induced activity and/ or ongoing sequences of fictive locomotion to varying degrees. These results suggest that neuropeptides play an important role in the control of the neural network for locomotion in the neonatal rat. Their various profiles of action may account in part for the great flexibility of motor behaviors.

Angiotensin II↗
PubMed2004

Identification of leucomyosuppressin in the German cockroach, Blattella germanica, as an inhibitor of food intake.

The feeding pattern of the adult female of Blattella germanica peaks in the middle of the vitellogenic cycle. Following the hypothesis that a factor inhibiting gut peristalsis also inhibits food intake and is involved in the regulation of feeding, we searched for the most powerful myoinhibitory peptide in brain extracts from B. germanica females collected after the peak within the feeding cycle. Through HPLC purification and sequence analysis, we obtained the peptide leucomyosuppressin (LMS): pQDVDHVFLRFamide. LMS elicited a powerful myoinhibitory effect on B. germanica foregut and hindgut, with ED(50) values around 10(-10) M. In addition, it inhibited food intake in vivo in a dose-dependent manner at doses between 5 and 50 microg. The study of the distribution of ingested food in the foregut, midgut and hindgut of B. germanica females treated with LMS showed that food accumulates in the foregut, which may be due to the myoinhibitory effects of the peptide. We propose that this accumulation inhibits food intake because of the persistence of the signals from gut stretch receptors.

Animals↗
PubMed2005

Hypotensive effect of novel chimeric peptides of met-enkephalin and FMRFa.

Endogenous opioid peptides like endomorphins, met-enkephalin and NPFF/FMRFamide family of neuropeptides, besides playing a role in modulation of antinociception, also affect cardiovascular system. Based on MERF, which consists of overlapping sequences of FMRFa and met-enkephalin, two chimeric peptides YGGFMKKKFMRFamide (YFa) and [D-Ala2] YAGFMKKKFMRFamide ([D-Ala2] YFa) were designed and synthesized. In this study, effect of YFa and [D-Ala2] YFa on arterial blood pressure and heart rate was evaluated in anaesthetized rats. Both YFa and [D-Ala2] YFa showed a dose-dependent fall in mean arterial pressure in dose-range of 13-78 micromol/kg. After naloxone treatment (5 mg/kg), vasodepressor effect of [D-Ala2] YFa and YFa was only partially blocked as compared to met-enkephalin. Partial blockade of vasodepressive effect of YFa and [D-Ala2] YFa by naloxone may be attributed to interaction of these chimeric peptides with receptors other than naloxone-sensitive receptors such as anti-opioid receptors, adrenergic receptors and D-analogue receptors.

Animals↗