In vivo effects of serotonin and fluoxetine on cardio-ventilatory functions in the shore crab Carcinus maenas (L. 1758).

Serotonin (5-HT) takes a key position in regulating vital functions, such as cardio-ventilatory activity, locomotion and behaviour. Selective serotonin reuptake inhibitors (SSRIs) modulate the serotonergic system and thus affect these functions. Rhythmic behaviours, such as cardio-ventilatory activity, are controlled by central pattern generators, which in turn are regulated by 5-HT.

Investigations of octylglyceryl dextran-graft-poly(lactic acid) nanoparticles for peptide delivery to the brain.

Aim: Develop modified dextran nanoparticles showing potential to assist with drug permeation across the blood-brain barrier for the delivery of neuropeptides.

Methods: Nanoparticles loaded by emulsification with model macromolecular actives were characterized in terms of stability, cytotoxicity and drug-release behavior. Peptide-loaded nanoformulations were tested in an in vivo trout model and in food-deprived mice.

Effects of peripherally administered urotensin II and arginine vasotocin on the QT interval of the electrocardiogram in trout.

The QT interval of the electrocardiogram (ECG) is a measure of the duration of the ventricular depolarization and repolarization. In fish as in human, the QT interval is positively correlated with the RR interval of the ECG, a measure of the cardiac cycle length. Urotensin II (UII) is a neuropeptide that has been highly conserved from fish to human, and UII and its receptor (UT) are expressed in cardiovascular tissues including the heart.

Hollow-layered nanoparticles for therapeutic delivery of peptide prepared using electrospraying.

The viability of single and coaxial electrospray techniques to encapsulate model peptide-angiotensin II into near mono-dispersed spherical, nanocarriers comprising N-octyl-O-sulphate chitosan and tristearin, respectively, was explored. The stability of peptide under controlled electric fields (during particle generation) was evaluated. Resulting nanocarriers were analysed using dynamic light scattering and electron microscopy.

Divergent cardio-ventilatory and locomotor effects of centrally and peripherally administered urotensin II and urotensin II-related peptides in trout.

The urotensin II (UII) gene family consists of four paralogous genes called UII, UII-related peptide (URP), URP1 and URP2. UII and URP peptides exhibit the same cyclic hexapeptide core sequence (CFWKYC) while the N- and C-terminal regions are variable. UII, URP1, and URP2 mRNAs are differentially expressed within the central nervous system of teleost fishes, suggesting that they may exert distinct functions.

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, urotensin II-related peptide, and their receptor: from structure to function.

Urotensin II (UII) is a cyclic neuropeptide that was first isolated from the urophysis of teleost fish on the basis of its ability to contract the hindgut. Subsequently, UII was characterized in tetrapods including humans. Phylogenetic studies and synteny analysis indicate that UII and its paralogous peptide urotensin II-related peptide (URP) belong to the somatostatin/cortistatin superfamily.

Central actions of serotonin and fluoxetine on the QT interval of the electrocardiogram in trout.

QT interval of the electrocardiogram (ECG) is a measure of the duration of the ventricular depolarization and repolarization. In humans, prolongation of the QT interval is a known clinical risk factor for the development of ventricular arrhythmias including ‘Torsades de Pointes’ and possible sudden cardiac death. After oral administration, fluoxetine (FLX), as well as other selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors can affect cardiac autonomic control, including the QT interval.

Effects of intracerebroventricular administered fluoxetine on cardio-ventilatory functions in rainbow trout (Oncorhynchus mykiss).

Fluoxetine (FLX) is a selective serotonin (5-HT) reuptake inhibitor present in the aquatic environment which is known to bioconcentrate in the brains of exposed fish. FLX acts as a disruptor of various neuroendocrine functions in the brain, but nothing is known about the possible consequence of FLX exposure on the cardio-ventilatory system in fish. Here we undertook to investigate the central actions of FLX on ventilatory and cardiovascular function in unanesthetized rainbow trout (Oncorhynchus mykiss).

Central ventilatory and cardiovascular actions of serotonin in trout.

This study was undertaken to investigate the central actions of 5-HT on ventilatory and cardiovascular variables in the unanesthetized trout. Compared to vehicle, intracerebroventricular injection (ICV) of 5-HT elevated the total ventilation. This elevation was due to its stimulatory action on ventilatory amplitude.

Central ventilatory and cardiovascular actions of trout gastrin-releasing peptide (GRP) in the unanesthetized trout.

Gastrin-releasing peptide (GRP), a neuropeptide initially isolated from porcine stomach, shares sequence similarity with bombesin. GRP and its receptors are present in the brains and peripheral tissues of several species of teleost fish, but little is known about the ventilatory and cardiovascular effects of this peptide in these vertebrates. The goal of this study was to compare the central and peripheral actions of picomolar doses of trout GRP on ventilatory and cardiovascular variables in the unanesthetized rainbow trout.

Brain neuropeptides in central ventilatory and cardiovascular regulation in trout.

Many neuropeptides and their G-protein coupled receptors (GPCRs) are present within the brain area involved in ventilatory and cardiovascular regulation but only a few mammalian studies have focused on the integrative physiological actions of neuropeptides on these vital cardio-respiratory regulations. Because both the central neuroanatomical substrates that govern motor ventilatory and cardiovascular output and the primary sequence of regulatory peptides and their receptors have been mostly conserved through evolution, we have developed a trout model to study the central action of native neuropeptides on cardio-ventilatory regulation. In the present review, we summarize the most recent results obtained using this non-mammalian model with a focus on PACAP, VIP, tachykinins, CRF, urotensin-1, CGRP, angiotensin-related peptides, urotensin-II, NPY, and PYY.

Central ventilatory and cardiovascular actions of angiotensin peptides in trout.

In the brains of teleosts, angiotensin II (ANG II), one of the main effector peptides of the renin-angiotensin system, is implicated in various physiological functions notably body fluid and electrolyte homeostasis and cardiovascular regulation, but nothing is known regarding the potential action of ANG II and other angiotensin derivatives on ventilation. Consequently, the goal of the present study was to determine possible ventilatory and cardiovascular effects of intracerebroventricular injection of picomole doses (5-100 pmol) of trout [Asn(1)]-ANG II, [Asp(1)]-ANG II, ANG III, ANG IV, and ANG 1-7 into the third ventricle of unanesthetized trout. The central actions of these peptides were also compared with their ventilatory and cardiovascular actions when injected peripherally.

Central ventilatory and cardiovascular actions of calcitonin gene-related peptide in unanesthetized trout.

Calcitonin gene-related peptide (CGRP) and its receptors are widely distributed in the tissues of teleost fish, including the brain, but little is known about the ventilatory and cardiovascular effects of the peptide in these vertebrates. The present study was undertaken to compare the central and peripheral actions of graded doses (5-50 pmol) of trout CGRP on ventilatory and cardiovascular variables in unanesthetized rainbow trout. Compared with vehicle, intracerebroventricular injection of CGRP significantly elevated the ventilation frequency (f(V)) and the ventilation amplitude (V(AMP)) and, consequently, the total ventilation (V(TOT)).

Central pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) decrease the baroreflex sensitivity in trout.

Although PACAP and VIP exert diverse actions on heart and blood vessels along the vertebrate phylum, no information is currently available concerning the potential role of these peptides on the regulation of the baroreflex response, a major mechanism for blood pressure homeostasis. Consequently, the goal of this study was to examine in our experimental model, the unanesthetized rainbow trout Oncorhynchus mykiss, whether PACAP and VIP are involved in the regulation of the cardiac baroreflex sensitivity (BRS). Cross-spectral analysis techniques using a fast Fourier transform algorithm were employed to calculate the coherence, phase and gain of the transfer function between spontaneous fluctuations of systolic arterial blood pressure and R-R intervals of the electrocardiogram.

Urotensin II, from fish to human.

The cyclic peptide urotensin II (UII) was originally isolated from the urophysis of teleost fish on the basis of its ability to contract intestinal smooth muscle. The UII peptide has subsequently been isolated from frog brain and, later on, the pre-proUII cDNA has been characterized in mammals, including humans. A UII paralog called urotensin II-related peptide (URP) has been identified in the rat brain.

Central effects of trout tachykinins on heart rate variability in trout.

Recent studies in trout have shown that tachykinins might be selectively implicated in important neuroregulatory functions related to the central control of ventilation. In teleost fish, cardiorespiratory coupling probably contributes to heart rate variability (HRV), and the hypoventilatory effects observed after central injection of tachykinins suggest that these peptides also may produce changes in HRV. Consequently, the present study was undertaken to compare the central actions of picomolar doses (25-250 pmol) of trout neuropeptide gamma (NPgamma), substance P (SP), and neurokinin A (NKA) on HRV in unanesthetized rainbow trout.

Central hyperventilatory action of the stress-related neurohormonal peptides, corticotropin-releasing factor and urotensin-I in the trout Oncorhynchus mykiss.

The stress-related neurohormonal peptides corticotropin-releasing factor (CRF) and urotensin-I (U-I), an ortholog of mammalian urocortin 1, are widely distributed in the central nervous systems of teleost fish but little is known about their possible central neurotropic actions. In the present study, we investigated the effect of intracerebroventricular (ICV) injection of CRF and U-I (1-10pmol) on ventilatory and cardiovascular variables in our established unanaesthetized trout model. CRF and U-I produced a significant dose-dependent and long-lasting increase in the ventilatory frequency (VF) and the ventilatory amplitude (VA).

Central cardiovascular actions of angiotensin II in trout.

In mammals, a large body of evidence supports the existence of a brain renin-angiotensin system (RAS) acting independently or synergistically with the endocrine RAS to maintain diverse physiological functions, notably cardiovascular homeostasis. The RAS is of ancient origin and although most components of the RAS are present within the brain of teleost fishes, little is known regarding the central physiological actions of the RAS in these vertebrates. The present review encompasses the most relevant functional data for a role of the brain RAS in cardiovascular regulations in our experimental animal model, the unanesthetized trout Oncorhynchus mykiss.

Ventilatory and cardiovascular actions of centrally administered trout tachykinins in the unanesthetized trout.

The brains of teleost fish contain members of the tachykinin family that are the products of orthologous genes expressed in mammalian nervous tissues, but little is known regarding the physiological effects of these peptides in their species of origin. The present study compares the central actions of trout neuropeptide gamma (NPgamma), substance P (SP) and neurokinin A (NKA) (5-250 pmol) on ventilatory and cardiovascular parameters in the unanesthetized rainbow trout Oncorhynchus mykiss. Intracerebroventricular (ICV) injection of NPgamma evoked a dose-dependent elevation of the ventilation rate (f(V)) but a reduction of the ventilation amplitude (V(AMP)) that was caused by a reduction of the magnitude of the adduction phase of the ventilatory signal.

Central and peripheral cardiovascular, ventilatory, and motor effects of trout urotensin-II in the trout.

Urotensin-II (U-II) was originally considered to be exclusively the product of the caudal neurosecretory system (CNSS) of teleost fish, but it has now been demonstrated that U-II is widely expressed in peripheral tissues and nervous structures of species from lampreys to mammals. However, very little is known regarding the physiological effects of this peptide in its species of origin. In the present review, we summarize the most significant results relating to the cardiovascular, ventilatory, and motor effects of centrally and peripherally administered synthetic trout U-II in our experimental animal model, the unanesthetized trout Oncorhynchus mykiss.

Central actions of angiotensin II on spontaneous baroreflex sensitivity in the trout Onc orhynchus mykiss.

The goal of the present study was to investigate the central action of native angiotensin II (ANG II) on the spontaneous baroreflex sensitivity (BRS) in unanesthetized trout. The animals were equipped with two subcutaneous electrocardiographic (ECG) electrodes, a dorsal aorta catheter and an intracerebroventricular (ICV) cannula which was inserted within the third ventricle of the brain. The ECG and the systolic blood pressure (SBP) signals were recorded during a pre-injection period of 5 min and during five post-injection periods of 5 min.

Cardiovascular actions of the stress-related neurohormonal peptides, corticotropin-releasing factor and urotensin-I in the trout Oncorhynchus mykiss.

In this review, we summarize the most significant data concerning the cardiovascular effects of centrally and peripherally administered synthetic trout corticotropin-releasing factor (CRF) and urotensin-I (U-I) in our animal model, the unanesthetized trout Oncorhynchus mykiss. Although there is more than 60% sequence identity between these two stress-related neurohormonal peptides, CRF and U-I-induced differential actions upon the mean dorsal aortic blood pressure (Pda) and the heart rate (HR) in trout maintained under similar experimental situations. After intracerebroventricular injections, only U-I induced an increase in Pda while in non-cannulated trout, CRF only decreased the HR and elevated the heart rate variability by a presumed activation of the parasympathetic nervous system activity to the heart.

Central effects of native urotensin II on motor activity, ventilatory movements, and heart rate in the trout Oncorhynchus mykiss.

Urotensin II (UII) has been originally isolated from fish urophysis. However, in fish as in mammals, UII is also produced in brain neurons. Although UII binding sites are widely distributed in the fish central nervous system (CNS), little is known regarding its central activities.

Captopril blocks the cardiac actions of centrally administered angiotensin I in the trout Oncorhynchus mykiss.

The present study was performed in order to gain new insights into the existence of a brain renin-angiotensin system (RAS) in teleost fish. For this purpose, we investigated the effects of centrally administered angiotensin (ANG) I ([Asn(1),Val(5),Asn(9)]ANG I) and ANG II ([Asn(1),Val(5)]ANG II) on heart rate (HR) and heart rate variability (HRV) in the unanesthetized trout. The animals were studied before and after treatment with captopril, an angiotensin-converting enzyme (ACE) inhibitor.