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Biomedical subjects

W H Watson

Publications and source records attributed to W H Watson.

At least 37 records · Page 2Linked to original sources

Peptidergic regulation of the Limulus midgut.

1. The morphology and innervation of the midgut (intestine) in the horseshoe crab, Limulus polyphemus was investigated. The organization of this tissue was examined with routine histology. Radioimmunoassay, immunohistochemistry and high performance liquid chromatography were employed to detect, localize and identify peptidergic innervation of the midgut. The actions of synthetic and native proctolin-like and FMRFamide-like peptides were compared on the isolated midgut preparation. 2. Levels of proctolin and FMRFamide were determined in extracts of Limulus midgut tissue using radioimmunoassay. High levels of proctolin-like immunoreactivity (69.5 +/- 11.3 ng/g) were detected, while levels of FMRFamide-like immunoreactivity (0.8 +/- 0.2 ng/g) were less. Proctolin levels were equally distributed, while the levels of FMRFamide-like immunoreactivity exhibited an anterior bias. 3. Proctolin- and FMRFamide-like immunoreactivities in the Limulus midgut were localized with immunohistochemistry. Proctolin- and FMRFamide-immunoreactive elements were detected in intestinal nerve branches and individual fibers running along the surface of the midgut in whole-mount preparations. In sectioned tissue, staining for these peptides was observed throughout the midgut, typically associated with muscle bands and fibers. Only a few immunoreactive cell bodies were observed. 4. Proctolin, and several FMRFamide-like peptides produced distinct and opposing actions on the isolated Limulus midgut preparation. Proctolin elicited contracture and rhythmic contractions of this tissue, while FMRFamide and N-terminally extended analogs of FLRFamide relaxed gut tension. FMRFamide-like peptides partially reversed the excitatory actions of proctolin. 5. Proctolin- and FMRFamide-like peptides in Limulus midgut extracts were partially characterized with high performance liquid chromatography. One peak of proctolin-like activity was detected on a linear gradient of 18 to 31.5% acetonitrile. The native proctolin-like peptide produced excitatory actions on the isolated midgut preparation which were indistinguishable from those produced by synthetic proctolin. Several peaks of FMRFamide-like bioactivity (Busycon radula protractor muscle assay) were detected with a linear gradient of 5 to 30% acetonitrile. Fractions from two distinct peaks produced FMRFamide-like inhibitory effects on the isolated Limulus midgut preparation. These findings suggest a role for proctolin-like and FMRFamide-like peptides as regulators of intestinal motility in Limulus.

Animals↗

Structure of the flavone hymenoxin.

2-(3,4-Dimethoxyphenyl)-5,7-dihydroxy-6,8-dimethoxy-4H-chromen-4-o ne, C19H18O8, Mr = 374.38, monoclinic, P2(1)/n, a = 9.026(4), b = 15.054(6), c = 12.829(6) A, beta = 100.98(4) degrees, V = 1711(1) A3, Z = 4, Dx = 1.450 g cm-3, lambda (Mo K alpha) = 0.71073 A, mu = 1.07 cm-1, F(000) = 784, T = 295 K, R = 0.0778 for 2280 independent reflections. The nearly planar AB ring system (0.04 A r.m.s.d.), O(1) to C(10), and the planar C ring (0.001 A r.m.s.d.) are almost coplanar with an interplanar angle of only 4.4(4) degrees. The methyl groups at C(6) and C(8) are rotated out of the molecular plane on opposite sides with torsion angles C(5)C(6)O(6)C(11) = -94.5(4) and C(7)C(8)O(8)C(12) = 109.0(4) degrees. The methyl groups of ring C are coplanar with the ring, C(3')C(4')O(4')"(13) = 0.2(5) and C(6')C(5')O(5')C(14) = 1.3(5) degrees. The carbonyl group forms an intramolecular hydrogen bond with O(5), O(5)...O(4) = 2.612(5), H(5O)...O(4) = 1.85(4) A, O(5)-H(5O)...O(4) = 151.9(8) degrees, and an intermolecular hydrogen bond with O(7) of an adjacent molecule, O(7)...O(4) (-0.5 + x, -0.5 - y, 0.5 + z) = 2.689(5), H(7O)...O(4) = 1.92(4) A, and O(7)-H(7O)...O(4) = 163.2(8) degrees.

Flavonoids↗

Involvement of cyclic AMP in multiple, excitatory actions of biogenic amines on the cardiac ganglion of the horseshoe crab Limulus polyphemus.

Cyclic AMP appears to be involved in several excitatory actions of amines on neurones of the Limulus cardiac ganglion. Amines selectively increase levels of cardiac ganglion cyclic AMP with a magnitude and time course similar to that observed for amine-induced excitation of cardiac ganglion burst rate. With respect to either the physiological or biochemical effect, the apparent order of potency is octopamine greater than epinephrine approximately dopamine greater than norepinephrine. Elevation of cardiac ganglion cyclic AMP levels by octopamine or dopamine is dose-dependent and is potentiated by the phosphodiesterase inhibitor 3-isobutyl 1-methylxanthine (IBMX). Several pharmacological agents which influence cyclic nucleotide metabolism, including forskolin, IBMX and 8-substituted cyclic AMP analogues, have amine-like effects on the Limulus cardiac ganglion. These effects include increased burst rate of the isolated cardiac ganglion and decreased burst duration, interburst interval and number of spikes per burst in follower neurones. Forskolin and IBMX increase levels of cardiac ganglion cyclic AMP, and IBMX also increases cyclic GMP levels in this tissue. Amines, forskolin and IBMX have direct effects on follower neurones pharmacologically isolated from pacemaker cell input. Octopamine, forskolin and IBMX depolarize follower neurones, while dopamine hyperpolarizes these cells. Amines, forskolin and IBMX elicit burst-like potentials in follower neurones, and increase the size of evoked, unitary junction potentials recorded in cardiac muscle fibres. These pharmacological and biochemical data suggest that multiple, excitatory effects of biogenic amines on the Limulus cardiac ganglion are mediated by simultaneous increases in cyclic AMP at several loci within this neural network.

1-Methyl-3-isobutylxanthine↗

Second-messenger systems underlying amine and peptide actions on cardiac muscle in the horseshoe crab Limulus polyphemus.

The biochemical mechanisms by which octopamine, catecholamines and the peptide proctolin exert their actions on Limulus cardiac muscle were investigated. Amines produced long-lasting increases in the amplitude of contractions evoked by electrical stimulation. At 10(-5) mol l-1, the apparent order of potency for amine-induced increases in evoked contraction amplitude was dopamine approximately equal to octopamine greater than norepinephrine approximately equal to epinephrine. At this dose, amines produced long-lasting increases in the levels of cyclic AMP (octopamine greater than dopamine approximately equal to norepinephrine approximately equal to epinephrine), but not of cyclic GMP, in Limulus cardiac muscle. Like the amines, the adenylate cyclase activator forskolin enhanced cardiac muscle contractility and increased levels of cyclic AMP, but not of cyclic GMP. The phosphodiesterase inhibitor IBMX produced a transient increase in cardiac muscle contractility, but typically produced long-lasting negative inotropy. This agent increased levels of both cyclic AMP and cyclic GMP in Limulus cardiac muscle. Proctolin and the protein kinase C activator phorbol dB increased the contraction amplitude of the intact heart and the electrically stimulated myocardium. These compounds, as well as dopamine, elicited sustained contractures and rhythmic contractions when applied to deganglionated Limulus cardiac muscle rings. Unlike the amines, proctolin and phorbol dB did not increase cardiac muscle cyclic AMP levels. These results suggest that several second-messenger systems may be utilized by amines and peptides to produce excitatory actions on cardiac muscle fibers of the Limulus heart. Cyclic AMP appears to be an important second messenger underlying the effects of amines to enhance cardiac muscle contractility. Pharmacological data suggest that proctolin may alter cardiac muscle contractility and excitability by a mechanism which involves the phosphatidylinositol pathway. Dopamine, unlike the other amines, produces a number of proctolin-like effects and may activate both the cyclic AMP and the phosphatidylinositol systems in Limulus cardiac muscle.

1-Methyl-3-isobutylxanthine↗

The molluscan neuropeptide, SCPB, increases the responsiveness of the feeding motor program of Limax maximus.

Small cardioactive peptide B (SCPB) has an excitatory effect on both buccal neurons and musculature in numerous molluscan species. The present study reports the effects of SCPB on the activity of specified buccal neurons and the expression of the feeding motor program of the terrestrial slug, Limax maximus. Superfusion of an isolated CNS preparation with 10(-6)M SCPB results in a 3-4-fold increase in the burst frequency of the fast salivary burster neuron (FSB), while having no effect on the activity of another endogenous burster, the bilateral salivary neuron (BSN). The response of the FSB to SCPB is dose dependent, with a threshold concentration of 2 X 10(-8)M. The response of the FSB to SCPB showed no indication of desensitization, even after long-term exposure (20 min). The feeding motor program (FMP) in Limax is a discrete pattern of cyclical motor activity that can be initiated by lip nerve stimulation. In the presence of SCPB a previously subthreshold stimulus can initiate the full FMP. The pattern of the FMP, once initiated, appears unaffected by SCPB. Thus it is the responsiveness of the initiation process that is enhanced by SCPB. Histochemical studies revealed a number of buccal neuron somata and fibers that stain for SCPB-like immunoreactive material (SLIM).

Action Potentials↗

Rating disabilities of older patients by nurses and social workers on geriatric health care teams: a research note with implications for further study.

This article reports the results of an analysis of interprofessional agreements between nurses and social workers when rating older patients on their physical self-maintenance abilities, mental statuses, and dispositions to social interaction with other residents of a home for the aged. The findings showed statistically significant intercorrelations of ratings of physical self-maintenance abilities and mental statuses, but no agreement on disposition to interaction. These findings are interpreted for their implications for research and practices of nurses and social-workers on geriatric health care teams.

Activities of Daily Living↗

Mechanism for amine modulation of the neurogenic Limulus heart: evidence for involvement of cAMP.

The role of cyclic nucleotides as intracellular second messengers mediating the excitatory chronotropic and inotropic actions of octopamine (OCT) and dopamine (DA) on the neurogenic Limulus heart was investigated. Tissue levels of cAMP, but not cGMP, were significantly increased in isolated cardiac ganglia and cardiac muscle following 10 min exposure to 10(-5) M OCT or 10(-5) M DA. In both tissues, OCT elicited larger increases in cAMP than did DA. Amine-induced cAMP accumulation in the cardiac ganglion and in the cardiac muscle was prevented by the alpha-adrenergic blocker phentolamine. The adenylate cyclase activator forskolin and the phosphodiesterase inhibitor IBMX produced amine-like chronotropic and inotropic effects when applied to the isolated heart preparation. However, the kinetics of the responses differed for the two agents. Additional pharmacological agents (RO-20-1724, papaverine, SQ 20,009, and 8-parachloro-phenylthio cAMP) also had amine-like effects but to a lesser extent. The chronotropic, but not inotropic, effects of OCT and DA were potentiated in the presence of IBMX. These data suggest that a cAMP-dependent mechanism underlies the excitatory effects of the neuromodulators OCT and DA on the Limulus heart.

1-Methyl-3-isobutylxanthine↗

Proctolin induces rhythmic contractions and spikes in Limulus heart muscle.

The Limulus heart is neurogenic. If the cardiac ganglion is removed, all spontaneous contractions of the heart are abolished. Application of the pentapeptide proctolin (greater than 1 microM) causes the deganglionated heart muscle to beat with a frequency and amplitude slightly greater than those of a normal heart with an intact cardiac ganglion. At a proctolin concentration of 1 microM, rhythmic beating requires 2-10 min to develop, and up to 1 h of continuous washing is required to reverse the effect. A contracture often precedes the rhythmic contractions. Proctolin-induced rhythmicity occurs in the presence of tetrodotoxin (TTX) and in Na+-free saline. These effects of proctolin are not mediated by residual portions of the cardiac ganglion. Contractions are inhibited by Ca2+-free EGTA saline, CoCl2, MnCl2, and CdCl2. Proctolin causes no significant long-term changes in the myocardial resting potential or apparent input resistance. However, proctolin causes rhythmic 10- to 20-mV spikes that precede each contraction of the myocardium. Production of these spikes appears to be the mechanism by which proctolin causes rhythmic contractions in normally quiescent deganglionated myocardium of Limulus.

Action Potentials↗

Neurohormonal modulation of the Limulus heart: amine actions on neuromuscular transmission and cardiac muscle.

The responses of Limulus cardiac neuromuscular junctions and cardiac muscle cells to four endogenous amines were determined in order to identify the cellular targets underlying amine modulation of heartbeat amplitude. The amines increased the amplitude of the Limulus heartbeat, with dopamine (DA) being more potent than octopamine, epinephrine or norepinephrine. The effect of DA on heartbeat amplitude was not blocked by phentolamine. DA enhanced the contractility of deganglionated heart muscle, with time course and dose-dependence similar to its effect on the intact heart. The amines also enhanced neuromuscular transmission, with time course and dose-dependence similar to their effects upon the intact heart. The amplitude of unitary excitatory junction potentials (EJPs) and frequency of miniature excitatory junction potentials (mEJPs) were increased by DA, while mEJP amplitude was unchanged. Thus DA, and probably the other amines, had a presynaptic effect. Combined actions upon cardiac muscle and cardiac neuromuscular transmission account for the ability of these amines to increase the amplitude of the Limulus heartbeat.

Amines↗

Identification and localization of catecholamines in the nervous system of Limulus polyphemus.

The concentrations of various catecholamines in the nervous system of the horseshoe crab Limulus polyphemus have been determined by high-performance liquid chromatography with electrochemical detection. Dopamine, norepinephrine, epinephrine, and their precursor L-Dopa were present in appreciable quantities in discrete regions of the central nervous system and cardiac ganglion. The catecholamines were localized more precisely by use of the glyoxylic-acid-histofluorescence technique of de la Torre and Surgeon (1976). Catecholamine fluorescence appeared in protocerebral and tritocerebral neuropile, including regions of the central body and optic medulla. Posterior to these brain areas, tracts extended through the circumesophageal ganglionic ring and laterally out each of the pedal ganglia. Small clusters of large fluorescent somata were present in the protocerebrum. No fluorescence was observed in the corpora pedunculata.

Animals↗

Amine modulation of the neurogenic Limulus heart.

(1) The biogenic amines octopamine (OCT), dopamine (DA), epinephrine (E), and norepinephrine (NE) cause dose-dependent increases in both the rate and amplitude of contractions of the isolated Limulus heart-cardiac ganglion. Their relative ability to produce this excitation is OCT greater than DA approximately the same as E greater than NE. (2) The excitatory effects of all these amines are antagonized by the alpha-adrenergic blocker phentolamine and the dopaminergic antagonist haloperidol. The beta-adrenergic antagonist dichloroisoproterenol slightly reduces amine excitation, but is also a partial agonist. The beta-adrenergic antagonist propanolol, the alpha-blocker phenoxybenzamine, and the serotonin antagonist metergoline are ineffective. (3) In addition to their excitatory effects, DA and, to a lesser extent, NE initially reduce contraction rate and amplitude. (4) The transient inhibition is eliminated selectively by metergoline and is unaffected by the other antagonists. (5) The amines all increase the frequency of cardiac ganglion electrical bursting activity, whether ganglia are isolated or attached to cardiac muscle. Dopamine and NE also transiently inhibit the cardiac ganglion. (6) The amines do not alter myocardial resting tension, contractility, or membrane potential. (7) These amines appear to exert their modulatory effects on Limulus heart by altering the properties of the neurons which comprise its cardiac ganglion.

Animals↗

The neuropeptide proctolin acts directly on Limulus cardiac muscle to increase the amplitude of contraction.

The pentapeptide proctolin increases the amplitude of contraction but not heart beat frequency of the isolated heart of Limulus polyphemus. It acts directly on the heart muscle and has no effects on the neurones of the cardiac ganglion or on the cardiac neuromuscular EJPs. A peptide with molecular weight, enzymatic susceptibilities and physiological effects similar to those of proctolin occurs in the Limulus cardiac ganglion. It is suggested that proctolin, or a family of proctolin-like peptides, may modulate muscle contraction in more than one subphylum of the Arthropoda.

Animals↗

Antibiotics from basidiomycetes. XIII. The alliacols A and B from Marasmius alliaceus (Jacq. ex Fr.) Fr.

Two antimicrobial and cytotoxic metabolites were isolated from fermentation broth of Marasmius alliaceus. The structures of the two crystalline antibiotics, alliacols A (6) and B (1) were elucidated by spectroscopic methods and chemical correlation with alliacolide (3). The alliacols show weak antibacterial and antifungal activity. Both antibiotics strongly inhibit DNA synthesis in cells of the ascitic form of Ehrlich carcinoma at concentrations of 2 approximately 5 microgram/ml. Both alliacols A and B react with cysteine to form adducts with strongly reduced biological activities.

Anti-Bacterial Agents↗