Mode of action of somatostatin to inhibit secretion by shark rectal gland

1985 ◽  
Vol 249 (3) ◽  
pp. R329-R334 ◽  
Author(s):  
P. Silva ◽  
J. S. Stoff ◽  
D. R. Leone ◽  
F. H. Epstein

The rectal gland of the spiny dogfish Squalus acanthias is stimulated to secrete chloride by vasoactive intestinal peptide (VIP) in a way that is inhibited by somatostatin. The mechanism of inhibition by somatostatin was studied in isolated perfused rectal glands and separated rectal gland cells. Somatostatin did not alter the specific binding of VIP to rectal gland cells but inhibited their accumulation of adenosine 3',5'-cyclic monophosphate (cAMP) in response to VIP. In isolated perfused glands, somatostatin inhibited the stimulation of secretion produced by VIP, adenosine, and forskolin, as well as by dibutyryl cAMP plus a phosphodiesterase inhibitor. The results support the hypothesis of both a proximal and a distal locus, in the cascade of events leading from adenylate cyclase activation to cellular response, at which somatostatin exerts an inhibitory effect.

2020 ◽  
Vol 319 (1) ◽  
pp. R96-R105
Author(s):  
Rolf Kinne ◽  
Katherine C. Spokes ◽  
Patricio Silva

The rectal gland of the spiny dogfish Squalus acanthias secretes a salt solution isosmotic with plasma that maintains the salt homeostasis of the fish. It secretes salt against an electrochemical gradient that requires the expenditure of energy. Isolated rectal glands perfused without glucose secrete salt, albeit at a rate about 30% of glands perfused with 5 mM glucose. Gradually reducing the glucose concentration is associated with a progressive decrease in the secretion of chloride. The apparent Km for the exogenous glucose-dependent chloride secretion is around 2 mM. Phloretin and cytochalasin B, agents that inhibit facilitated glucose carriers of the solute carrier 2 (Slc2) family such as glucose transporter 2 (GLUT2), do not inhibit the secretion of chloride by the perfused rectal glands. Phloridzin, which inhibits Slc5 family of glucose symporters, or α-methyl-d-glucoside, which competitively inhibits the uptake of glucose through Slc5 symporters, inhibit the secretion of chloride. Thus the movement of glucose into the rectal gland cells appears to be mediated by a sodium-glucose symporter. Sodium-glucose cotransporter 1 (SGLT1), the first member of the Slc5 family of sodium-linked glucose symporters, was cloned from the rectal gland. No evidence of GLUT2 was found. The persistence of secretion of chloride in the absence of glucose in the perfusate suggests that there is an additional source of energy within the cells. The use of 2-mercapto-acetate did not result in any change in the secretion of chloride, suggesting that the oxidation of fatty acids is not the source of energy for the secretion of chloride. Perfusion of isolated glands with KCN in the absence of glucose further reduces the secretion of chloride but does not abolish it, again suggesting that there is another source of energy within the cells. Glucose was measured in the rectal gland cells and found to be at concentrations in the range of that in the perfusate. Glycogen measurements indicated that there are significant stores of glucose in the rectal gland. Moreover, glycogen synthase was partially cloned from rectal gland cells. The open reading frame of glycogen phosphorylase was also cloned from rectal gland cells. Measurements of glycogen phosphorylase showed that the enzyme is mostly in its active form in the cells. The cells of the rectal gland of the spiny dogfish require exogenous glucose to fully support the active secretion of salt. They have the means to transport glucose into the cells in the form of SGLT1. The cells also have an endogenous supply of glucose as glycogen and have the necessary elements to synthesize, store, and hydrolyze it.


2008 ◽  
Vol 63 (9-10) ◽  
pp. 773-779 ◽  
Author(s):  
Ana Maneva ◽  
Borislava Taleva

The aim of the present study was to assess if some flavonic compounds (quercetin, piceatannol and apigenin) and ascorbic acid could interfere with the Lf stimulatory effect on the erythrocyte function. Quercetin (1.5 μm) and piceatannol (30 μm) showed an additive effect on Lf stimulation of Na+/K+-ATPase when used together with Lf. The enhancement of Lf stimulation on Na+/K+-ATPase in the presence of flavonoids was probably due to their antioxidative properties and/or to their involvement in the erythrocyte signaling. None of the estimated flavonoids showed an effect on Lf stimulation of the lactate production. Quercetin itself enhanced the ATPase activity but did not affect the lactate formation. Apigenin (1.5 μm) enhanced reliably the lactate generation, but it did not exert any effect on the ATPase activity. High concentration of ascorbic acid (60 mm) did not change the Lf stimulatory effect on Na+/K+-ATPase, but decreased the Lf-specific-binding. A significantly strong inhibitory effect on the Lf-specific binding exerted the electron acceptors NAD+ (2 mm) and FAD (2 mm). These effects concern most likely the competition with Lf for electron(s) which is (are) provided from the erythrocyte intercellular electron transport chain(s).


1983 ◽  
Vol 106 (1) ◽  
pp. 25-41 ◽  
Author(s):  
F. H. Epstein ◽  
J. S. Stoff ◽  
P. Silva

Secretion of chloride from blood to lumen is accomplished in the rectal gland of elasmobranchs by a process of secondary active transport involving the co-transport of Cl- with Na+ across the basolateral membranes of rectal gland cells. Energy is provided by ATP via membrane Na-K-ATPase, which establishes an electrochemical gradient favouring Na+ influx into the cell. The involvement of K+ in the co-transport mechanism, so as to provide a ratio of 1 Na+:1 K+:2 Cl- entering the cell, would increase the energetic efficiency of the process, and is consistent with the Cl/O2 ration of 27–30 observed in secreting rectal glands. Secretion is stimulated by cyclic AMP (cAMP) and by vasoactive intestinal peptide (VIP) and adenosine, which activate adenylate cyclase. Activation of the gland in vivo probably occurs via VIP-secreting nerves as well as circulating agents; it is inhibited by somatostatin. Cyclic AMP probably stimulates chloride secretion by at least three mechanisms: (1) increasing chloride conductance across the luminal cell membrane, (2) enhancing the co-transport pathway for transmembrane movements of Na+, K+ and Cl- and (3) activating Na-K-ATPase.


1999 ◽  
Vol 277 (6) ◽  
pp. R1725-R1732 ◽  
Author(s):  
Patricio Silva ◽  
Richard J. Solomon ◽  
Franklin H. Epstein

We studied the modes of activation of the salt-secreting rectal gland of the spiny dogfish, Squalus acanthias, by the native cardiac peptide CNP. The stimulatory action of CNP in isolated perfused glands is inhibited by 10 mM procaine, presumably by blocking release of vasoactive intestinal peptide (VIP) from nerves. Procaine reduces the slope of the dose-response curve of human CNP and that of shark CNP (each P < 0.0001). CNP increases short-circuit current in cultured rectal gland cells from 4.8 ± 1.6 to 27.0 ± 7.8 μA/cm2. It also stimulates the secretion of chloride in isolated perfused glands in the presence of 10 mM procaine from 72 ± 31 to 652 ± 173 μeq ⋅ h−1 ⋅ g−1. These results suggest that CNP has a direct cellular action not mediated by the neural release of VIP. The residual stimulation of perfused glands in the presence of procaine was almost completely inhibited by staurosporine [10 nM; an inhibitor of protein kinase C (PKC)] from 652 ± 173 to 237 ± 61 μeq ⋅ h−1 ⋅ g−1. Although CNP stimulates guanylyl cyclase in shark rectal gland, chloride secretion of perfused glands was not elicited by 8-bromoadenosine-cGMP (8-BrcGMP) alone nor by the activator of PKC phorbol ester. The combination of PKC activation and 8-BrcGMP infusion, however, stimulated chloride secretion in perfused glands from 94 ± 30 to 506 ± 61 μeq ⋅ h−1 ⋅ g−1, a level comparable to that observed in glands blocked with procaine. Several parallel pathways appear to be synergistic in activating chloride secretion stimulated by CNP in the rectal gland.


1990 ◽  
Vol 1025 (1) ◽  
pp. 21-31 ◽  
Author(s):  
Arnost Kleinzeller ◽  
George W. Booz ◽  
John W. Mills ◽  
Fuad N. Ziyadeh

1990 ◽  
Vol 258 (6) ◽  
pp. R1459-R1463
Author(s):  
P. Silva ◽  
S. Lear ◽  
S. Reichlin ◽  
F. H. Epstein

The function of bombesin-like peptide, a neurotransmitter present in nerve fibers of elasmobranch rectal glands, is unknown. Since the principal activity of the rectal gland is to secrete chloride, the effects of bombesin on chloride secretion and the role of somatostatin in this response was studied. Bombesin failed to stimulate secretion in rectal glands perfused in the basal state. When added to glands stimulated by a constant infusion of vasoactive intestinal peptide (VIP), bombesin (8 x 10(-7) M) reversibly inhibited chloride secretion by 56 +/- 9.7% and at the same time evoked a 10-fold increase in the liberation of somatostatin into the venous effluent. Inactivation of somatostatin by the addition of cysteamine partially suppressed the inhibitory effect of bombesin on glandular secretion. The effect of bombesin to reduce chloride secretion was completely prevented by the calcium channel blocker nifedipine, which inhibits neurotransmitter release. These results suggest that bombesin inhibits the effect of VIP to stimulate chloride secretion by releasing somatostatin from neurosecretory nerve terminals within the rectal gland.


1992 ◽  
Vol 262 (4) ◽  
pp. R707-R711 ◽  
Author(s):  
R. Solomon ◽  
A. Protter ◽  
G. McEnroe ◽  
J. G. Porter ◽  
P. Silva

Homologous shark C-type natriuretic peptide (sCNP) was infused as a bolus and as a constant infusion in the isolated perfused rectal gland of the same species, Squalus acanthias. sCNP was a potent stimulator of chloride secretion similar in its dose-response curve to vasoactive intestinal peptide. sCNP was equipotent with killifish CNP but more potent than human CNP (hCNP). Truncated and substituted, forms of hCNP were also capable of stimulation of chloride secretion in the order hCNP greater than hCNP (6-22) = [Gly9]hCNP greater than hCNP-(7-21). sCNP was more potent than human atrial natriuretic peptide (hANP), which was more potent than porcine brain natriuretic peptide. hANP-(31-67) was without effect. These studies suggest that sCNP may be the physiological regulator of rectal gland function. The receptor in the rectal gland is unknown but based on the order of potencies, position 4 in the NH2-terminal end and the ring itself are important for ligand effects.


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