Potentiation by Endotoxin of Responses Associated with Increases in Calcium Conductance

Abstract

Bacterial endotoxin at concentrations of and synapses. We present evidence that in four different preparations, each of which depends for a certain response on increases in calcium conductance, endotoxin enhanced the physiologic response. These preparations and responses are: (1) tonic contraction of smooth muscle from a dogfish mesentery; (2) postsynaptic response in squid giant fiber synapses; (3) response of lobster and crayfish muscle fibers to direct stimulation; and (4) calcium current in frog atrial muscle fibers. Dogfish mesenteric muscleThe mesenteric smooth muscle of a dogfish can give either brief phasic or prolonged tonic contractions in response to either electrical or mechanical stimulation; these responses are determined by action potentials that appear to result from increases in calcium conductance (7). Phasic contraction is associated with a single action potential, and tonic contraction with repetitive muscle spikes; these responses occur in the presence of tetrodotoxin, an agent that selectively blocks the regenerative sodium conductance increase in nerve and muscle (8), and result from direct stimulation of the muscle. Effects of endotoxin were tested on 12 preparations. Muscle strips were mounted in a 30-ml bath so that contractions were recorded with a force transducer and action potentials by floating microelectrodes (for details see ref. 7). Each muscle was initially stimulated with pulses of 5-msec duration at 60-sec intervals so that only repeated phasic contractions of constant amplitude were obtained (9); then endotoxin was added to the bath to give final concentrations of 0.03-0.1 jig/ ml. Fig. 1 shows that endotoxin enhanced contraction and caused a preparation that was giving only phasic contractions (Fig. 1A) to go into prolonged tonic contractions (Fig. 1B and C). The enhancement was noted within 2-5 min and reached a maximum at 5-10 min. During the tonic contraction, rhythmic action potentials were observed (Fig. 1C). The enhanced smooth muscle response due to endotoxin was reversible by washing and could be repeated several times on the same preparation. Addition of corticosteroids (methylprednisolone, Solu-Medrol, Upjohn, or Decadron, Merck) at concentrations of 0.1 ,ug/ml caused immediate recovery from the endotoxin effect ( Fig. iD and H). If a preparation was pretreated with steroid, the endotoxin was ineffective. It is possible that endotoxin may act by way of autonomic nerve endings since the dogfish muscle is sensitive to norepinephrine by way of

Endotoxaemia and complement activation in acute pancreatitis in man.

“…Patients with pancreatitis are prone to develop hypoxia, hypotension, renal failure, hypocalcaemia, and disseminated intravascular coagulation as complications.6 All of these changes can be produced experimentally by endotoxaemia.7 8 Patients who die of pancreatitis commonly have evidence of shock lung and, recently, complement activation has been associated with the development of this syndrome.9…”

Toxic interactions of benzyl alcohol with bacterial endotoxin

“…Furthermore, benzyl alcohol inhibits clearance by hepatocytes of asialo-glycoproteins by acting as a selective inhibitor of fusion of lysosomes and endocytic vesicles (55). In light of the Ca2+ involvement in endotoxicosis (16,24,30,44), it is important to note that benzyl alcohol stimulates Ca2+ uptake (10) and activates Ca2'-dependent enzymes (2,56).…”

Factors Influencing Calcium Influx in Endotoxin-Challenged Fibroblasts

“…The concentration of calcium in the culture medium is known to affect the growth of several cell types, including fibroblasts (1 [3][4][5][6][7][8][9][10][11][12][13][14][15]. Besides, several lines of studies suggest that a marked increase in the intracellular calcium concentration could lead to cell death (16)(17)(18)(19)(20)(21)(22)(23).…”