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T J Shuttleworth

Publications and source records attributed to T J Shuttleworth.

50 records · Page 3Linked to original sources

Secretory activity in salt glands of birds and turtles: stimulation via cyclic AMP.

O2 consumption in tissue slices from the nasal salt gland of the duck and the lachrymal salt gland of Malaclemys is stimulated by methacholine, a stimulation that is inhibited by bumetanide and by ouabain. In addition, the calcium ionophore A23187 mimics the action of methacholine in stimulating this secretion-related O2 consumption in both glands, suggesting a second-messenger role for this ion in the cholinergic response. However, the adenylate cyclase activator, forskolin, and the cyclic AMP analogue, 8-cpt-cAMP, also stimulate ouabain-sensitive and bumetanide-sensitive O2 consumption in both the duck gland and the Malaclemys gland. It is suggested that the mechanism of salt secretion in the Malaclemys lachrymal gland conforms to that previously described for other extrarenal salt-secreting tissues in nonmammalian vertebrates and, as in the bird gland, is subject to a cholinergic regulation potentially acting via changes in intracellular calcium. In addition to this, secretory activity in both the avian and the turtle glands can be stimulated by a previously undisclosed adenylate cyclase-cyclic AMP system. The identity of the primary signal for such a system is not known, nor is the nature of any interrelationship between the two second-messenger systems that have been identified in these glands.

Animals↗

Potassium secretion by nasal salt glands of desert lizard Sauromalus obesus.

Potassium secretion by the nasal salt glands of the herbivorous desert lizard Sauromalus obesus was determined in vivo by a new technique. Intraperitoneal injection of KCl rapidly increased the potassium secretion rate from 0.28 to 15.35 mumol X 100 g-1 X h-1. A second identical intraperitoneal injection, given 15 h after the first, further increased potassium secretion to 50.09 mumol X 100 g-1 X h-1. This was associated with a doubling of plasma K+ concentration and salt gland Na+-K+-adenosinetriphosphatase (ATPase) activity. Neither salt gland weight or residual (Mg2+) ATPase activity were affected. In an isolated perfused head preparation, potassium secretion from the nasal salt glands was stimulated from 0.99 to 10.76 mumol X 100 g-1 X h-1 by methacholine and to 14.68 mumol X 100 g-1 X h-1 by forskolin. In this perfused preparation, simultaneous determination of salt gland perfusion flow (using radiolabeled microspheres) and the rate of potassium secretion revealed that the secreting glands removed 68% of the perfusing potassium ions. Calculations indicated that secretion at the maximal rate observed in vivo would necessitate a fourfold increase in the rate of blood flow to the gland.

Adenosine Triphosphatases↗

Mode of adrenergic and peptidergic inhibition of ion transport in flounder gill.

The mechanisms of inhibition of branchial ion transport by epinephrine and somatostatin were investigated in the isolated perfused gill preparation of seawater-adapted flounder Platichthys flesus. The electrogenic transepithelial potential recorded in gills perfused and bathed with identical salines was stimulated by glucagon, forskolin, or a cyclic adenosine 5' monophosphate (AMP) derivative, each administered at a concentration identified in preliminary experiments as being submaximally effective. The subsequent abilities of epinephrine and somatostatin to inhibit the stimulated potential were found to be dependent on the site of action of the stimulatory agent with respect to the formation of cyclic AMP. Thus the maximal adrenergic or peptidergic inhibition of the potential stimulated by exogenous cyclic AMP was significantly reduced compared with the maximal inhibition of the potential stimulated by either forskolin or glucagon. The data indicate dual modes of action by which epinephrine and somatostatin achieve maximal inhibition of branchial ion transport; a cyclic AMP-independent mechanism that is effective in the presence of cyclic AMP and an additional mechanism to inhibit cyclic AMP synthesis.

Animals↗

Perfusion-secretion relationships in the isolated elasmobranch rectal gland.

Perfusion and sodium secretion parameters were measured in the isolated rectal gland of Scyliorhinus canicula L. perfused at in vivo pressures, and the effect of stimulation of secretory activity by cyclic AMP and theophylline on these parameters was determined. Stimulation resulted in large increases in secretion flow rate, percentage extraction of sodium from the perfusing fluid, and arteriovenous sodium concentration difference, but did not affect perfusion flow rate or the sodium concentration of the secreted fluid. Reduction of perfusion flow rate to values below 65% of the control level, achieved by reducing perfusion pressure, produced a marked decline in sodium secretion--a process accompanied by increases in the percentage extraction of sodium and arteriovenous concentration difference of sodium, but again without any change in the sodium concentration of the secreted fluid. The in vivo consequences of these findings are discussed with reference to related findings for the avian nasal salt gland. The normal rate of secretion, its sodium concentration, and the nature of the dependence of secretion rate on perfusion flow below certain levels, were essentially unaffected by a reduction in the availability of oxygen to the gland by approximately 80%. It is concluded that the observed relationship between perfusion flow and sodium secretion rate in the stimulated gland is not related to oxygen availability, and hence that the primary underlying function of the synchronized secretion-related vasodilation seen in the gland is not to increase the supply of oxygen to the stimulated secretory tissue. We discuss possible reasons why this erroneous conclusion has been reached by other workers.

Animals↗

Biochemical and physiological studies on peptides from the elasmobranch gut.

A peptide fraction has been purified from intestinal extracts of the dogfish Scyliorhinus canicula which is a powerful stimulant of rectal gland secretory activity. This peptide is distinct from elasmobranch vasoactive intestinal polypeptide (VIP). The elasmobranch VIP fraction is not active in the rectal gland assay and mammalian VIP is only an effective agonist in Squalus and not in Scyliorhinus or Raja. Preliminary characterisation of the elasmobranch VIP indicate that it has strong N-terminal similarities with mammalian VIP but has limited C-terminal comparability. It is suggested that the rectal gland stimulating peptide, rectin, rather than VIP is responsible for the control of fluid and electrolyte secretion of elasmobranchs.

Animals↗

Pancreatic peptides regulate Cl- secretion in the marine teleost gill.

Hormonal regulation of the ionoregulatory function of the branchial epithelium in marine teleosts has been investigated using an isolated gill preparation of the seawater-adapted flounder Platichthys flesus. Agents which are assumed to elevate the effective intracellular concentration of cyclic AMP caused a stimulation of Cl- secretion as determined by measurement of the transepithelial electrical potential difference in the isolated gill. The pancreatic endocrine glucagon may act as an endogenous regulator of ion excretion in the gill as this peptide stimulated the transepithelial potential. Another islet peptide, somatostatin, inhibited branchial electrogenic ion transport. Attempts to investigate the mode of action of these peptides by measuring cyclic AMP levels in isolated gills were unsuccessful, since it appears that the pool of cyclic nucleotide which specifies the epithelial Cl- transport rate is small compared to total cyclic AMP content. A second approach investigating the ability of somatostatin to inhibit the transepithelial potential in gills stimulated by different secretagogues suggested dual modes of action for this peptide.

Animals↗

An endogenous peptide stimulates secretory activity in the elasmobranch rectal gland.

Extraction and partial purification of peptide material from the intestine of the elasmobranch Scyliorhinus canicula yielded a fraction that shows potent stimulatory activity in the rectal gland. The extracted material appears to contain an endogenous peptide (or peptides) that represents the natural hormone responsible for the control of rectal gland secretion in vivo.

Animals↗

Beta-alanine transport in the isolated hepatocytes of the elasmobranch Raja erinacea.

Cells were isolated from the liver of the skate and the uptake of beta-alanine followed using [14C]-beta-alanine. The isolated hepatocytes showed good viability, were found to accumulate beta-alanine from the incubation medium, and did so in a manner indicating a transport system involving a saturable carrier. The data for the rate of beta-alanine uptake suggest that this may be a rate-limiting step in the oxidation of the amino acid by the liver. Experiments indicated that the transport system could distinguish beta-alanine from certain structurally similar molecules (L-alanine and taurine, but not gamma-amino butyrate). Cells isolated from fish adapted to a diluted environment (50% seawater) showed no significant change in the uptake rate. However, evidence indicates that, over the range of beta-alanine concentrations occurring in the fish, the uptake rate would be acutely sensitive to small changes in the concentration in the blood, thus forming a self-regulating system for the metabolism of beta-alanine.

Alanine↗

Hemodynamics and potentials in isolated flounder gills: effects of catecholamines.

Branchial hemodynamics and transepithelial potentials were investigated in an isolated perfused gill preparation from the flounder (Platichthys flesus L.). An analysis of the pressure-flow profiles suggests that the gill is compliant but that the physical relationships of pressure and flow are complex. Epinephrine has a bimodal effect with an initial vasoconstriction followed by a vasodilation, the latter response being much smaller than that usually seen in teleosts. Pharmacological analysis shows 1) an alpha-mediated vasoconstriction of the arterial and venous pathway, associated with a redistribution of flow away from the venous pathway, and 2) a small beta-mediated vasodilation of the arterial pathway only. An electrical potential (inside positive) was measured across the isolated gill, bathed and perfused with an identical saline. This potential was recorded, despite the venous system being open to the external bath, and was independent of both arterial and venous flows. Epinephrine caused a significant decline in this potential, which could be resolved into a large inhibitory alpha-mediated response and a small beta-mediated stimulation.

Animals↗

Role of calcium in cAMP-mediated effects in the elasmobranch rectal gland.

The effects of A23187 and verapamil on the vasomotor and secretory effects of adenosine 3',5'-cyclic monophosphate (cAMP) in the rectal gland were investigated in Scyliorhinus canicula and Squalus acanthias. A23187 was a potent vasoconstrictor in the gland and reversed the vasodilatory action of cAMP in glands constricted with norepinephrine. Verapamil, like cAMP, prevented the vasoconstriction induced in the gland by norepinephrine. A23187 had no effect on the secretory activity (measured as ouabain binding and ouabain-sensitive oxygen consumption) of the glands. Verapamil inhibited the stimulation of ouabain binding, ouabain-sensitive oxygen consumption, and sodium secretion rate induced by cAMP plus theophylline, but did not affect the stimulation of ouabain binding and ouabain-sensitive oxygen consumption induced by amphotericin B. These data indicate that it is the cAMP-induced stimulation of the sodium-chloride cotransport system that is verapamil sensitive, and it is suggested that this stimulation is a calcium-dependent process. This emphasizes the independent nature of the secretory and vasomotor effects of the nucleotide in the gland.

Amphotericin B↗

Haemodynamic effects of secretory agents on the isolated elasmobranch rectal gland.

Perfusion flow rate in the isolated elasmobranch rectal gland, perfused at in vivo pressures, was measured in Scyliorhinus canicula L. and Squalus acanthias L. Flow through the secretory parenchyma of the gland was reduced in the presence of concentrations of catecholamines in the physiological range, an effect mediated via alpha-adrenergic receptors within the gland vasculature. Flow through the non-secretory vascular shunts of the rectal gland was unaffected. The vasoconstriction induced by noradrenaline was blocked by the addition of cyclic AMP + theophylline or adenosine at concentrations known to stimulate secretion by the gland. In Squalus, a similar effect was seen with the secretagogue vasoactive intestinal peptide, but this agent had no effect in the glands of Scyliorhinus. Experiments indicate that the blockage of the noradrenaline effect by the secretory agents does not involve any stimulation of vasodilatory beta-adrenergic receptors and, furthermore, that the vasomotor effects of these agents appear to be entirely independent of their actions on the secretory cells. Evidence is presented indicating that the vasomotor action of adenosine may be mediated via receptors specific for the ribose moiety of the nucleoside (Ra receptors) activating adenylate cyclase, and that this may, in turn, explain the observed effects of the addition of exogenous cyclic AMP. The significance of the observed vascular effects in the overall control of secretion rate by the gland in vivo is discussed.

Animals↗

Amphotericin B and the elasmobranch rectal gland: implications for the relationship between oxygen consumption and ion transport.

In slices of the dogfish rectal gland, amphotericin B produced increases in oxygen consumption and ouabain binding similar to those produced by cyclic AMP, except that the increases induced by the latter were inhibited by furosemide whereas those resulting from the addition of amphotericin B were unaffected by the diuretic. Unlike cyclic AMP, however, amphotericin B failed to stimulate secretion by the isolated perfused gland. These results support the suggestion that the increases in ouabain binding and oxygen consumption produced by cyclic AMP result simply from an increased sodium entry into the cells, and as such can be mimicked by amphotericin B, whereas secretion rate itself depends on some additional, cyclic AMP-induced process. The implications of this for determinations of the relationship between rates of oxygen consumption and ion transport are discussed.

Amphotericin B↗