scholarly journals Investigation of the relationship between cell-surface calcium-ion gating and phosphatidylinositol turnover by comparison of the effects of elevated extracellular potassium ion concentration on ileium smooth muscle and pancreas

1976 ◽  
Vol 160 (2) ◽  
pp. 397-399 ◽  
Author(s):  
S S Jafferji ◽  
R H Michell
Keyword(s):  
Smooth Muscle ◽  
Cell Surface ◽  
Guinea Pig ◽  
Ion Concentration ◽  
Cholinergic Antagonists ◽  
Extracellular Potassium ◽  
Phosphatidylinositol Turnover ◽  
Contrast Exposure ◽  
Muscarinic Cholinergic ◽  
K Concentration

Incubation of fragments of guinea-pig ileum smooth muscle in the presence of an elevated extracellular K+ concentration, which causes an increase in cell-surface Ca2+ permeability and thus leads to contraction, caused a marked increase in phosphatidylinositol turnover, as assessed by incorporation of 32Pi. This response was not diminished by atropine or propylbenzilycholine mustard, two muscarinic cholinergic antagonists, and was therefore not caused by the release of endogenous acetylcholine within the tissue. In contrast, exposure of guinea-pig pancreas fragments to high extracellular [K+], which does not increase cell-surface Ca2+ permeability or evoke secretion, did not cause an increase in phosphatidylinositol turnover, even though such an increase was triggered by carbamoylcholine, which is a secretagogue. These observations are consistent with a suggested function for phosphatidylinositol breakdown in the mechanisms of cell-surface Ca2+ gates.

scholarly journals Effects of calcium-antagonistic drugs on the stimulation by carbamoylcholine and histamine of phosphatidylinositol turnover in longitudinal smooth muscle of guinea-pig ileum

1976 ◽  
Vol 160 (2) ◽  
pp. 163-169 ◽  
Author(s):  
S S Jafferji ◽  
R H Michell
Keyword(s):  
Smooth Muscle ◽  
Cell Surface ◽  
Guinea Pig ◽  
Guinea Pig Ileum ◽  
Receptor Antagonists ◽  
Sequence Of Events ◽  
Longitudinal Smooth Muscle ◽  
Phosphatidylinositol Turnover ◽  
Phosphatidylinositol Response ◽  
Sites Of Action

A number of drugs classed as calcium antagonists, spasmolytics, non-specific receptor antagonists or receptor antagonists with multiple sites of action were tested to determine whether they prevent the stimulation of phosphatidylinositol turnover caused in various tissues by the activation of receptors which increase cell-surface Ca2+ permeability. The experiments were done with fragments of longitudinal smooth muscle from guinea-pig ileum; these were incubated in vitro with 32Pi and either 100 muM-carbamoylcholine or 100 muM-histamine, in the presence of antagonistic drugs at concentrations at least sufficient to cause complete blockade of smooth-muscle contraction. The phosphatidylinositol response to carbamoylcholine was not changed by cinchocaine, papaverine, nifedipine, dibenamine, amethocaine, cinnarizine, lidoflazine, methoxyverapamil, prenylamine or two antimuscarinic alkane-bis-ammonium compounds, and the response to histamine was unaffected by the first four drugs. In contrast, phenoxybenzamine prevented the increase in phosphatidylinositol labelling caused by either carbamoylcholine or histamine. The insensitivity of the phosphatidylinositol response to most of the drugs provides further experimental support for the conclusion that the receptor-stimulated phosphatidylinositol breakdown which initiates the increase in phosphatidylinositol turnover is not caused by an increase in intracellular Ca2+. The simplest interpretation of the available information appears to be that phosphatidylinositol breakdown plays a role in the coupling between the receptor-agonist interaction and the opening of cell-surface Ca2+ gates [Michell, R. H. (1975) Biochim. Biophys. Acta 415, 81-147]. If this is correct, then phenoxybenzamine must exert its inhibitory effects on phosphatidylinositol breakdown early in this sequence of events, but the drugs must act at a stage later than phosphatidylinositol breakdown. The unexpected difference in the effects of dibenamine and phenoxybenzamine, which are chemically very similar, may provide a useful experimental tool with which to explore the way in which activated receptors provoke the opening of cell-surface Ca2+ gates.

scholarly journals Nexuses between the smooth muscle cells of the guinea-pig ileum.

1979 ◽  
Vol 82 (1) ◽  
pp. 239-247 ◽  
Author(s):  
G Gabella ◽  
D Blundell
Keyword(s):  
Smooth Muscle ◽  
Cell Surface ◽  
Guinea Pig ◽  
Smooth Muscle Cells ◽  
Muscle Cell ◽  
Packing Density ◽  
Freeze Fracture ◽  
Muscle Cells ◽  
Guinea Pig Ileum ◽  
Average Cell

The circular musculature of the guinea-pig ileum has been studied by freeze-fracture to analyze quantitatively the gap junctions (nexuses) between its smooth muscle cells. The average cell surface area and cell volume are 5,074 micron 2 and 3,260 micron 3. The packing density of nexuses is 48/1,000 micron 2 of cell surface or approximately 244/muscle cell. Nexuses range in area from less than 0.1 to approximately 1.5 micron 2 and they occupy 0.212% of the cell surface. The average packing density of intramembrane particles or pits in nexuses is approximately 7,200/micron 2 of nexal surface, indicating that there may be approximately 77,000 intercellular channels in the full complement of nexuses of one muscle cell.

Na+-K+-ATPase inhibition stimulates PGE release in guinea pig taenia coli

1977 ◽  
Vol 232 (5) ◽  
pp. C191-C195 ◽  
Author(s):  
R. F. Coburn ◽  
S. Soltoff
Keyword(s):  
Smooth Muscle ◽  
Plasma Membrane ◽  
Guinea Pig ◽  
Prostaglandin E ◽  
Taenia Coli ◽  
Na Pump ◽  
Membrane Enzyme ◽  
K Concentration ◽  
Atpase Inhibition ◽  
Prostaglandin E Release

Inhibition of the plasma membrane enzyme Na+-K+-ATPase by ouabain zero extracellular K+, or low extracellular Na+, markedly augmented prostaglandin E release from the guinea pig taenia coli. Data suggest this phenomenon may be linked directly to Na+-K+-ATPase or Na+ pump activities, or changes in intracellular K+ concentration. The augmented prostaglandin E release was not due to changes in intracellular Na+, Ca2+, pH, or membrane potential, resulting from Na+ pump inhibition. The characteristics of the plasma membrane may exert a control on prostaglandin E release in this smooth muscle.

scholarly journals Spontaneous Oscillations of Cytoplasmic Free Calcium Ion Concentration in Cultured Smooth Muscle Cells from Guinea Pig Ileum

1993 ◽  
Vol 63 (1) ◽  
pp. 83-91 ◽  
Author(s):  
Hisayuki Ohata ◽  
Toru Kawanishi ◽  
Megumi Kawanishi ◽  
Chikako Uneyama ◽  
Michihito Takahashi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Smooth Muscle Cells ◽  
Calcium Ion ◽  
Muscle Cells ◽  
Ion Concentration ◽  
Free Calcium ◽  
Guinea Pig Ileum ◽  
Cultured Smooth Muscle Cells ◽  
Calcium Ion Concentration

scholarly journals Stimulation of phosphatidylinositol turnover in various tissues by cholinergic and adrenergic agonists, by histamine and by caerulein

1979 ◽  
Vol 182 (3) ◽  
pp. 669-676 ◽  
Author(s):  
Lynne M. Jones ◽  
Shamshad Cockcroft ◽  
Robert H. Michell
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Lacrimal Gland ◽  
Plasma Membranes ◽  
Partial Agonist ◽  
Muscarinic Agonist ◽  
Guinea Pig Ileum ◽  
Phosphatidylinositol Response ◽  
Muscarinic Cholinergic ◽  
Stimulation Of

Studies are reported of the biochemical and pharmacological characteristics of the stimulation of phosphatidylinositol metabolism that is produced in appropriate target tissues by stimulation of various receptors that use Ca2+ as their second messenger. (1) Muscarinic cholinergic and α-adrenergic phosphatidylinositol responses were observed in rat lacrimal gland, and a response to caerulein was detected in the longitudinal smooth muscle of guinea-pig ileum. (2) The muscarinic cholinergic phosphatidylinositol response of rat lacrimal gland, like that of several other tissues, is not dependent on the availability of extracellular Ca2+. (3) Three phosphatidylinositol responses, namely to histamine in guinea-pig ileum smooth muscle, to α-adrenergic stimulation in rat vas deferens and to muscarinic cholinergic stimulation in rat lacrimal gland, were all found to involve phosphatidylinositol breakdown. (4) The stereospecificity of the muscarinic receptor responsible for the phosphatidylinositol response of guinea-pig pancreas was tested by using the two stereoisomeric forms of acetyl-β-methylcholine; the S-isomer was very much more active than the R-isomer in provoking both phosphatidylinositol breakdown and its labelling with 32P, as it is in provoking other physiological responses such as contractility or secretion. (5) Pilocarpine, a muscarinic partial agonist, provoked a significantly smaller phosphatidylinositol breakdown in rat parotid fragments than did carbamoylcholine, a potent muscarinic agonist. (6) All of these results are consistent with, but do not prove, a previously offered hypothesis that suggests that phosphatidylinositol breakdown is a reaction essential to stimulus–response coupling at a variety of cell-surface receptors that mobilize Ca2+ from and through the plasma membranes of target tissues.

scholarly journals Muscarinic cholinergic stimulation of phosphatidylinositol turnover in the longitudinal smooth muscle of guinea-pig ileum

1976 ◽  
Vol 154 (3) ◽  
pp. 653-657 ◽  
Author(s):  
S S. Jafferji ◽  
R H. Michell
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Phosphatidyl Inositol ◽  
Anticholinergic Drugs ◽  
Muscarinic Agonists ◽  
Guinea Pig Ileum ◽  
High Concentration ◽  
Longitudinal Smooth Muscle ◽  
Muscarinic Cholinergic ◽  
Stimulation Of

1. The metabolism of phosphatidylinositol and phosphatidate was investigated in fragments of longitudinal smooth muscle from guinea-pig ileum incubated with cholinergic and anticholinergic drugs. 2. Incorporation of Pi into these lipids was enhanced by acetylcholine and carbamoylcholine. 3. The receptor responsible for triggering this response was of the muscarinic type, since (a) the response was also produced by the muscarinic agonists acetyl-β-methylcholine, carbamoyl-β-methylcholine and pilocarpine, and (b) the response was prevented by atropine and prophylbenzilylcholine mustard, but not by tubocurarine. 4. Increased phosphatidylinositol labellin was clearly observed within 5 min in tissue treated with a high concentration of carbamoylcholine. 5. Halfmaximal stimulation of phosphatidylinositol labelling occurred at approx. 10 muM-muM-carbamoylcholine. 6. Incubation of muscle fragments with carbamoylcholine provoked a decrease in phosphatidylinositol concentration, as would be expected if phosphatidyl-inositol breakdown is the reaction controlled by agonists. 7. This information all appears consistent with the proposal that phosphatidylinositol breakdown may be a reaction intrinsic to the mechanisms of muscarinic cholinergic receptor systems.

Inhibition of peptidases potentiates enkephalin-stimulated contraction of gastric muscle cells

1991 ◽  
Vol 261 (3) ◽  
pp. G476-G484 ◽  
Author(s):  
D. Menozzi ◽  
Z. F. Gu ◽  
P. N. Maton ◽  
N. W. Bunnett
Keyword(s):  
Smooth Muscle ◽  
Cell Surface ◽  
Guinea Pig ◽  
Muscle Cells ◽  
Peptidase Activity ◽  
Maximal Contraction ◽  
Physical Relationship ◽  
Gastric Smooth Muscle ◽  
Gastric Muscle ◽  
Guinea Pig Stomach

Cell surface peptidases degrade enkephalins and thereby restrict the number of molecules available to activate receptors. The effects of peptidase inhibitors on degradation of enkephalins and on enkephalin-stimulated contraction of gastric smooth muscle cells were examined. Muscle cells dispersed from the guinea pig stomach degraded [Tyr1-3H] [Leu5]enkephalin (41.6 +/- 9.0% degradation at 60 min incubation, mean +/- SD, n = 4 animals). Amastatin (10 microM, an aminopeptidase inhibitor) inhibited degradation by 72.1 +/- 1.5% The residual peptidase activity was inhibited by phosphoramidon (1 microM, an endopeptidase EC 3.4.24.11 inhibitor) by 58.0 +/- 11.0%. [Tyr1-125I] [Met5]enkephalin was similarly degraded. Phosphoramidon (1 microM) inhibited the degradation of the aminopeptidase-resistant peptide [Tyr1-3H] [D-Ala2]-[Leu5]enkephalin by greater than 95%. [Met5]enkephalin, incubated with cells for 30 s, stimulated contraction [50% maximal contraction (EC50) 120 +/- 50 nM, n = 6]. Pretreatment of cells with phosphoramidon alone, amastatin alone, or phosphoramidon plus amastatin, caused 20-fold (EC50 6.5 +/- 1.1 nM), 2-fold (EC50 63 +/- 23 nM), and 100-fold (EC50 1.1 +/- 0.3 nM) increase in potency of [Met5]enkephalin, respectively. The results show that endopeptidase EC 3.4.24.11 and aminopeptidases contribute to degradation of enkephalins by gastric muscle cells. The rapidity and magnitude of the potentiating effects of the inhibitors on enkephalin-stimulated contraction suggest a close physical relationship between the peptidases and the enkephalin receptors.

Sign in / Sign up

Export Citation Format

Share Document