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Biomedical subjects

R D Hurst

Publications and source records attributed to R D Hurst.

46 records · Page 3Linked to original sources
PubMed1991

The therapeutic role of octreotide in the management of surgical disorders.

The long-acting somatostatin analogue, octreotide, has recently been made available for clinical use in the United States. This novel synthetic peptide possesses a broad spectrum of physiologic actions primarily involving the inhibition of a variety of gastrointestinal and endocrine functions. Such actions have been utilized in the management of a variety of surgical disorders. Current understanding of the indications and efficacy of this agent in the treatment of surgical disease is reviewed.

Amino Acid Sequence↗
PubMed1990

Evidence for differential effects of noradrenaline and somatostatin on intracellular messenger systems in rat islets of Langerhans.

The mechanisms involved in inhibition of insulin secretion by somatostatin and noradrenaline were compared in order to establish whether the receptors for these agents are coupled to similar effector systems in the pancreatic B cell. Both agents significantly reduced forskolin-induced adenylate cyclase activity in islet homogenates, although noradrenaline was more effective than somatostatin. The capacity of noradrenaline to inhibit insulin secretion was largely unaffected by agents that increase intracellular cyclic AMP, whereas the effect of somatostatin as an inhibitor was markedly reduced under these conditions. Both noradrenaline and somatostatin inhibited the stimulation of insulin secretion induced by K+ depolarization, but different mechanism were involved. Somatostatin significantly inhibited K(+)-stimulated 45Ca2+ efflux and influx in islets, while noradrenaline exerted only a minor influence on these processes. The data indicate that noradrenaline controls insulin secretion by a mechanism which operates beyond the level of intracellular messenger generation. In contrast, somatostatin exerts at least part of its inhibitory effect on insulin secretion by directly controlling islet cell Ca2+ influx in a manner which may be regulated by cyclic AMP.

Adenylyl Cyclases↗
PubMed1989

Effects of benextramine on the adrenergic inhibition of insulin secretion in isolated rat pancreatic islets.

Insulin secretion from isolated rat islets of Langerhans in the presence of 4 mM glucose averaged 2.26 +/- 0.20 (S.E.M.) ng/islet per 90 min and was significantly (P less than 0.001; n = 30) increased to 3.28 +/- 0.21 ng/islet per 90 min by the covalent alpha-adrenoceptor antagonist benextramine (10 microM). Glucose (20 mM) also increased the secretion rate (to 6.24 +/- 6.0 ng/islet per 90 min) but, under these conditions, the response was not further enhanced by benextramine. Clonidine and noradrenaline (1 nM-10 microM) each caused dose-dependent inhibition of glucose-induced insulin secretion which was maximal at 1 microM. Benextramine, when added simultaneously with the agonist, relieved, in a dose-dependent manner, the inhibition of secretion induced by either clonidine or noradrenaline with similar sensitivity. Even after a 30-min preincubation with benextramine the antagonist failed to differentiate between noradrenaline, adrenaline and clonidine with respect to inhibition of insulin secretion. In contrast to its effects on adrenergic responses, short-term treatment with benextramine did not significantly affect muscarinic-cholinergic receptor-mediated 45Ca2+ efflux from rat islets of Langerhans perifused in Ca2+-depleted medium. These data suggest that benextramine does not differentiate between clonidine and noradrenaline in rat islets of Langerhans but that it does show preference for alpha-adrenoceptors in this tissue.

Adrenergic alpha-Antagonists↗
PubMed1988

Dissociation between intracellular calcium mobilization and insulin secretion in isolated rat islets of Langerhans.

The neuropeptide bombesin provoked a dose-dependent stimulation of 45Ca2+ efflux from pre-loaded islets of Langerhans. This response occurred rapidly, was not sustained and did not depend on the presence of extracellular calcium, suggesting that it resulted from the mobilization of intracellular calcium stores. Under conditions when large increases in 45Ca2+ efflux were observed, bombesin completely failed to stimulate the rate of insulin secretion. Similar results were also obtained with the muscarinic cholinergic agonist, carbachol. The data suggest that the release of calcium from intracellular pools is not sufficient to induce an increase in insulin secretion in normal islet cells.

Animals↗
PubMed1986

Graft-versus-host disease induced by small bowel allografts. Clinical course and pathology.

The histopathological changes and the course of graft-versus-host (GVH) disease were studied in the rat model of small-bowel transplantation using the Lewis----LBN-F1 strain combination. Allograft-induced GVH disease led to the recipients' death from enteritis, dermatitis and emaciation after 14.4 +/- 2.9 days (heterotopic grafts) and 14.0 +/- 0.7 days (orthotopic grafts). Histologic evidence of dermatitis (epidermal hyperkeratosis and cutaneous infiltration by mononuclear and polymorphonuclear cells) and enteritis (villous blunting and sloughing, inflammatory infiltrate of the recipient's own intestine) appeared on the 9th to 13th postoperative days, and these changes became fulminant within 2-3 days. The lymphatic tissues of the Lewis grafts and the LBN-F1 host underwent a course of progressive lymphoid depletion and loss of follicular architecture beginning on the 5th postoperative day. Throughout the postoperative course, the small-bowel graft remained intact. The relative spleen weight progressively increased until shortly before death, when a marked reduction was observed. The clinical triad of diarrhea, diffuse dermatitis, and hypertrophy of the lymphoid organs followed by their atrophy suggests a diagnosis of GVH disease rather than rejection of the small-bowel allograft. The diagnosis can be confirmed by biopsy of a recipient lymph node or the intestinal allograft (cave perforation) if it is accessible.

Animals↗
PubMedDate not supplied

Transmembrane signalling of cholinergic-stimulated contraction in isolated rat glomeruli.

Exposure of isolated rat glomeruli to carbachol (Carb) 1 mM induces glomerular (mesangial cell) contraction which is inhibited by pirenzepine. To identify the cellular signalling mechanism, we analyzed Carb-activated phosphoinositide hydrolysis in myo-[2-3H] inositol preloaded cells of isolated rat glomeruli. Carb evoked a rapid (5 s, 30.4 +/- 8.3% of basal) and sustained (60 s, 157.2 +/- 1.2% of basal) inositol trisphosphate (IP3) response. Acetylcholine 100 microM (Ach) in the presence of eserine also evoked IP3 formation. Mobilization of Ca2+ was monitored by preloading glomerular cells with 45Ca2+ (200 microCi/ml) and analyzing the cellular efflux using a constant perifusion system. Both Carb and Ach induced transient 45Ca2+ efflux, with peak values above baseline of 69.0 +/- 19.9 and 71.5 +/- 7.9%, respectively. Incubation with pirenzepine or prior release of Ca2+ from an IP3-sensitive intracellular pool by Thapsigargin (2 microM) prevented Carb-evoked Ca2+ release (100 and 60%, respectively). Therefore, glomerular cells possess functional cholinergic receptors which stimulate contraction via IP3-mediated intracellular Ca2+ release.

Acetylcholine↗
PubMedDate not supplied

Calcium modulation of the effects of serotonin, carbachol, and histamine on rabbit ileal ion transport.

In mammalian intestine, a number of secretagogues have been shown to work through either cyclic nucleotide or calcium mediated pathways to elicit ion secretion. Because excessive intestinal electrolyte and fluid secretion is central to the pathogenesis of a variety of diarrheal disorders, understanding of these processes is essential to the development of future clinical treatments. In the current study, the effects of serotonin (5HT), histamine, and carbachol on intestinal ion transport were examined in in vitro preparations of rabbit ileum. All three agonists induced a rapid and transient increase short-circuit current (delta Isc) across ileal mucosa. Inhibition of the delta Isc response of all three agents in chloride-free solution or in the presence of bumetanide confirmed that chloride is the main electrolyte involved in electrogenic ion secretion. Pretreatment of tissue with tetrodotoxin or atropine did not effect secretagogue-mediated electrolyte secretion. While tachyphylaxis of delta Isc response was shown to develop after repeated exposure of a secretagogue to tissue, delta Isc responses after sequential addition of different agonists indicate that cross-tachyphylaxis between agents did not occur. Serotonin, histamine, and carbachol have previously been reported to mediate electrolyte secretion through calcium-dependent pathways. To access the role of extracellular calcium in regulating ion secretion, the effect of verapamil on each agent was tested; verapamil decreased 5HT-induced delta Isc by 65.2% and histamine response by 33.5%, but had no effect on carbachol-elicited chloride secretion. An additive secretory effect was found upon simultaneous exposure of 5HT and carbachol to the system; no other combination of agents produced a significant additive effect. Findings from this study support previous work which has suggested that multiple calcium pathways may be involved in mediating chloride secretion in mammalian intestine.

Animals↗