Identification of opioid receptors in the sympathetic and parasympathetic nerves of guinea-pig atria (original) (raw)
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Peripheral sympatho-inhibitory cardiovascular effects of opioid peptides in anaesthetized rabbits
British Journal of Pharmacology, 1988
Opioid agonists influence isolated cardiovascular tissues from rabbits, as well as the cardiovascular system of pithed rabbits, through presynaptic receptors on postganglionic sympathetic nerve fibres. The present experiments were carried out in order to study effects which result from activation of these receptors in anaesthetized rabbits. 2 In pithed rabbits with electrically stimulated sympathetic outflow, infusion of [D-Ala2-D-Leu5]enkephalin (DADLE) 10 yg kg-'min-1 and dynorphin-l-13) (dynorphin) 1 pgkg-1 min-1 decreased the plasma noradrenaline concentration, mean arterial pressure (MAP) and heart rate. The effects of dynorphin and, less completely, those of DADLE were antagonized by the peripherally selective opioid antagonists N-methyl naloxone bromide (NMN) 1.3mgkg-1 and N-methyl levallorphan methanesulphonate (NML) 1-3 mg kg-. 3 In pentobarbitone-anaesthetized rabbits, DADLE 3-30ygkg-1 min-1 and dynorphin 0.3-3 g kg-1 min-1 decreased the plasma noradrenaline concentration and MAP. The highest dose of dynorphin also decreased heart rate, whereas DADLE l0ygkg-'min-' caused slight cardioacceleration. The effects of DADLE but not those of dynorphin decreased upon repeated administration. 4 The effects of dynorphin 10pgkg-'min-' were abolished or greatly attenuated by NMN 1.3mgkg-' and NML 3mgkg-'. In contrast, the antagonists reduced only slightly the blood pressure-lowering effect of DADLE 10pgkgmin-' and did not reduce significantly the effects of DADLE on the plasma noradrenaline level and heart rate. 5 It was concluded that systemically administered dynorphin produces sympatho-inhibition and an ensuing fall in blood pressure by an action at peripheral receptors, in all probability presynaptic K-receptors on postganglionic sympathetic nerve fibres. The effects of DADLE are more complex and may involve both central and peripheral components.
Clinical and Experimental Pharmacology and Physiology, 1989
I. Two strains of rabbits have been bred with marked differences in their cardiac baroreflex sensitivity (BRS). The difference in cardiac BRS was attenuated by naloxone. We compared the sympathetic responses to a pressor stimulus in these two strains, by measuring the changes in plasma catecholamines in the presence and absence of naloxone. 2. Cardiac BRS was assessed in eight rabbits of each group by the steady-state method. Two weeks later, both ear arteries and one ear vein were cannulated. Mean arterial pressure (MAP) and heart rate (HR) were recorded from one artery and blood samples (5 mL) for plasma catecholamines (CA) taken before, and during the peak of the pressor response to intravenous phenylephrine (PE, 20 pg/kg) from the other. The experiment was repeated 2-3 weeks later in rabbits with high BRS (Group I) after injection of naloxone 0.1 mg/kg, i.v. 3. Resting MAP and HR did not differ in the two groups. The mean gains of the cardiac baroreflex were 23.3-t 2.2 ms/mmHg in Group I and 6.3 k I. 1 ms/mmHg in Group 11. After PE, MAP rose by 54.5 * 1.8 mmHg in Group I1 and 40.3 t 3.6 mmHg in Group I (Pt0.02). The pressor response was associated with a 3 I % reduction in plasma noradrenaline (NA) in Group I and a 34% increase in Group 11. The reduction in NA was significantly correlated with the degree of bradycardia in Group I (r=0.72, Pt0.05) and with BRS in both groups (r=0.78, PtO.01). Naloxone reduced BRS in Group I to 8.2 f 1.0 ms/mmHg and virtually abolished the fall in plasma NA in response to PE. 4. We suggest that stimulation of cardiopulmonary afferents by a strong pressor stimulus in Group I rabbits results in sympathetic inhibition which involves the mediation of opioid peptides.
Presynaptic opioid receptors in the portal vein of the rabbit
European Journal of Pharmacology, 1987
The effects of opioids on sympathetic neuroeffector transmission were studied in superfused strips of the portal vein of the rabbit. In the first series of experiments, the tissue was stimulated electrically every 10 min with 10 pulses at 8 Hz and a current strength of 200 mA. The contractions evoked were concentration dependently inhibited by the slightly x-selective agonist ethylketocyclazocine and by the 8-selective agonists [D-Ala2,D-LeuS]enkephalin (DADLE) and [D-Pen2,D-PenS]enkephalin (DPDPLE). The/~-selective agonist [D-Ala2,NMePhe4,Gly-olS]enkephalin (DAGO) had no effect. The estimated ECs0 values for ethylketocyclazocine and DADLE were 5.5.10-8 and 2.9.10-8 tool/l, respectively. Naloxone shifted the concentration-response curves of ethylketocyclazocine and DADLE to the right; the estimated K b values were (1.7 + 0.4). 10-8 mol/1 and (2.9 + 0.8). 10-8 mol/1, respectively. The 8-selective antagonist ICI 174864 antagonized only the inhibitory effect of DADLE but not that of ethylketocyclazocine. In the second series of experiments, the tissue was preincubated with [3H]noradrenaline then superfused and stimulated electrically three times for 3 rain at 1 Hz and a current strength of 100 mA. Ethylketocyclazocine and DADLE inhibited the evoked overflow of tritium. The inhibition produced by ethylketocyclazocine was antagonized by naloxone. Our results show for the first time that opioid agonists inhibit noradrenaline release and hence, neurogenic vasoconstriction in a vein. As in other cardiovascular tissues of the rabbit, the presynaptic opioid receptors are of the x-and 8-but not the /~-type.
Autonomic Neuroscience, 2001
Electroacupuncture EA is used in traditional Chinese medicine to treat arrhythmias, hypertension and myocardial ischemia. Our Ž. previous work suggests that the inhibitory effect of EA on the pressor reflex induced by bradykinin BK applied to the gallbladder is due, Ž. in part, to the activation of opioid receptors, most likely located in the rostral ventrolateral medulla rVLM. However, specific opioid Ž receptor subtypes, and hence the neurotransmitters, responsible for this inhibition are unknown. Therefore, in anesthetized cats, BK 10. Ž. Ž mgrml was applied to the gallbladder to induce transient reflex increases in arterial blood pressure BP. EA 1-2 mA, 5 Hz, 0.5 ms. pulses was delivered through acupuncture needles inserted bilaterally into Neiguan and Jianshi acupoints on forelimbs, overlying the median nerves. EA attenuated the BK-induced pressor response by 39%. Opioid receptor subtype antagonists or agonists were microinjected unilaterally into the rVLM. The mand d-receptor antagonists CTOP and ICI 174,864, respectively, significantly attenuated Ž. the EA-induced inhibition for at least 30 min. The k-receptor antagonist nor-BNI was less effective and was shorter acting. Like EA, microinjection of mand d-opioid agonists, DAGO and DADLE, respectively, into the rVLM significantly decreased the pressor responses. In contrast, the k-opioid agonist, U50,488, failed to alter the BK-induced pressor response. We conclude that a significant portion of inhibition of the gallbladder pressor response by EA is related to activation of mand d-opioid receptors in the rVLM. The endogenous neurotransmitters for mand d-opioid receptors, b-endorphins and enkephalins, in the rVLM, therefore appear to play a role in the EA-related modulation of cardiovascular reflex responses. Conversely, dynorphin is less likely to be involved in this response.
The Journal of Comparative Neurology, 2001
Agonists of the -opioid receptor (MOR) produce profound hypotension and sympathoinhibition when microinjected into the rostral ventrolateral medulla (RVL). These effects are likely to be mediated by the inhibition of adrenergic and other presympathetic vasomotor neurons located in the RVL. The present ultrastructural studies were designed to determine whether these vasomotor neurons, or their afferents, contain MORs. RVL bulbospinal barosensitive neurons were recorded in anesthetized rats and filled individually with biotinamide by using a juxtacellular labeling method. Biotinamide was visualized by using a peroxidase method and MOR was identified by using immunogold localization of an antipeptide antibody that recognizes the cloned MOR, MOR1. The subcellular relationship of MOR1 to RVL neurons with fast-or slowconducting spinal axons was examined by electron microscopy. Fast-and slow-conducting cells were not morphologically distinguishable. Immunogold-labeling for MOR1 was found in all RVL bulbospinal barosensitive neurons examined (9 of 9). MOR1 was present in 52% of the dendrites from both types of cells and in approximately half of these dendrites the MOR1 was at nonsynaptic plasmalemmal sites. A smaller portion of biotinamide-labeled dendrites (16%) from both types of cells were contacted by MOR1-containing axons or axon terminals. Together, these results suggest that MOR agonists can directly influence the activity of all types of RVL sympathoexcitatory neurons and that MOR agonists may also influence the activity of afferent inputs to these cells. The heterogenous distribution of MORs within individual RVL neurons indicates that the receptor is selectively targeted to specific pre-and postsynaptic sites.
Opiate and peptide inhibition of transmitter release in parasympathetic nerve terminals
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1989
Somatostatin, morphine, and opioids inhibit transmitter release at intact neuromuscular junctions between ciliary ganglion neurons and the choroidal smooth muscle of the chick eye. Somatostatin and morphine, however, have no effect on release from terminals on the striated muscle target of the ciliary ganglion, the iris. In neuronal terminals of both the choroid and the iris, a high-affinity Na+-dependent choline uptake-mediated ACh synthesis is present at hatching. Both tissues exhibit a basal release of 3H-ACh which is potentiated severalfold during a 5 minute incubation in 55 mM K+ Tyrodes. Fifty percent of the basal release and 100% of the stimulated release are Ca2+ dependent and probably mediated through N-like voltage-dependent Ca2+ channels. Co-incubation of the choroid with 10 microM morphine sulfate blocks approximately 90% of the stimulated release. The same effect is seen with 100 nM somatostatin, 10 microM dynorphin, and 100 microM met-enkephalin arginine phenylalanine....
American Journal of Obstetrics and Gynecology, 1998
We sought to test the hypothesis that an intravenous dose of H-Tyr-D-Arg-Phe-Lys-NH2, a highly µ-receptor selective opioid peptide, suppresses baroreflex sensitivity through a peripheral mechanism. STUDY DESIGN: A transient change in mean arterial pressure was produced in chronically instrumented pregnant ewes by norepinephrine or sodium nitroprusside in the absence or in the presence of H-Tyr-D-Arg-Phe-Lys-NH2, a highly µ-selective opioid peptide. In some studies naloxone methiodide, a peripheral opioid antagonist, was infused starting 60 minutes before the administration of H-Tyr-D-Arg-Phe-Lys-NH2 and maintained for a total of 90 minutes. Linear plots were obtained when the changes in mean arterial pressure during the pressure rise were plotted against the changes in heart rate and the sensitivity of the baroreflex was derived as the slope of the linear regression line. RESULTS: We observed (1) lower baroreflex sensitivity after H-Tyr-D-Arg-Phe-Lys-NH2 administration with a hypertensive stimulus; (2) unchanged baroreflex sensitivity after H-Tyr-D-Arg-Phe-Lys-NH2 administration with a hypotensive stimulus; and (3) unchanged baroreflex sensitivity after H-Tyr-D-Arg-Phe-Lys-NH2 administration with a hypertensive stimulus in the presence of naloxone methiodide. CONCLUSION: H-Tyr-D-Arg-Phe-Lys-NH2 suppresses the hypertensive but not the hypotensive arm of the baroreflex through peripheral opioid receptors. These results suggest that µ-opioid receptors are present in the vagus nerves and that the activation of these opioid receptors inhibits reflex bradycardia in pregnant sheep.
Journal of Neurophysiology, 2003
Most parasympathetic regulation of heart rate originates from preganglionic cardiac vagal neurons within the nucleus ambiguus. Little is known regarding the modulation of glycinergic transmission to these neurons. However, the presence of µ-opioid receptors and ORL 1 receptors within the ambiguus, together with the presence of endogenous ligands for both receptor types in the same area suggests opioids may modulate synaptic transmission to cardiac vagal neurons. The present study therefore examined the effects of endomorphin-1 and endomorphin-2 (the µ-selective endogenous peptides), DAMGO (a synthetic, µ-selective agonist) and nociceptin (the ORL 1 -selective endogenous peptide) upon spontaneous glycinergic IPSCs in rat cardiac parasympathetic neurons.
BioMed research international, 2015
The differential effects of a selective kappa- (κ-) opioid receptor agonist, U50488, were elucidated by monitoring the contraction of isolated guinea pig atrial and ventricular muscles. In electrically driven left atria, U50488 in nanomolar concentration range decreased the contractile force. Norbinaltorphimine (norBNI), a selective κ-receptor antagonist, and pertussis toxin (PTX) abolished the negative inotropic effect of U50488. In contrast, the inhibitory effect was not affected by the pretreatment of atropine or propranolol. Even though U50488 exerted a negative inotropic effect in the left atrium, it did not affect the contractile force of the right atrium and ventricles paced at 2 Hz. Similarly, the beating rate of the spontaneously beating right atrium was also unaffected by U50488. These results indicate that the activation of κ-opioid receptors can only produce negative inotropic effect in left atria via activation of PTX-sensitive G protein in guinea pigs. The absence of n...