Z. Woskowska

Peptide YY stimulates circular muscle contractions of the isolated perfused canine ileum by inhibiting nitric oxide release and enhancing acetylcholine release

Peptide YY (PYY) and neuropeptide Y (NPY), infused into the quiescent isolated perfused canine ileum, dose-dependently increased phasic activity of the circular muscle and decreased tonic output of immunoreactive vasoactive intestinal peptide (VIP) in the venous effluent. The contractions subsided before the prolonged inhibition of VIP output. Motor excitation by PYY, an abundant neuropeptide in this tissue, was reduced by blockade of muscarinic or nicotinic receptors, or inhibition of nitric oxide (NO) synthase, despite continued inhibition of VIP output. A combination of atropine and hexamethonium eliminated the PYY-induced decrement in VIP output and left motor excitation unchanged. Blockade of NO synthase eliminated motility increases under these conditions. Intracellular microelectrode recordings of myenteric plexus-free circular muscle strips found no effect of NPY on the resting membrane potential, or on the field stimulation-induced inhibitory junction potential. Inhibition of VIP release plays no essential role in changing motility. These results suggest that PYY/NPY induce motility by stimulating release of acetylcholine and inhibiting NO release at a locus proximal to but not on nerve terminals.

Galanin inhibition of vasoactive intestinal polypeptide release and circular muscle motility in the isolated perfused canine ileum

The role of porcine galanin, infused arterially into isolated perfused canine ileal segments, in modulating the tonically elevated neural release of vasoactive intestinal polypeptide and possible concomitant motor actions dependent on vasoactive intestinal polypeptide modulation was studied. Galanin infusions (9-minute) inhibited vasoactive intestinal polypeptide release in a concentration-dependent manner (maximum during minutes 8-10) irrespective of the absence (quiescence) or presence of phasic circular muscle contractions induced by local electrical field stimulation of nerves. During quiescence, galanin induced phasic contractions in four of five segments beginning in the 8th minute of the infusion. During stimulated contractions, galanin inhibited phasic motor activity within 2 minutes of initiation of the infusion; this inhibition may result from direct smooth previously reported muscle inhibition. Thus galanin may inhibit both neural release of vasoactive intestinal polypeptide and circular muscle motility directly. The delayed period of phasic activity initiated by galanin during quiescence may be related to inhibition of vasoactive intestinal polypeptide release, freeing the muscle from tonic inhibition by vasoactive intestinal polypeptide. Because galanin and vasoactive intestinal polypeptide are colocalized in some enteric nerves, galanin may regulate vasoactive intestinal polypeptide release by negative feedback.

Consumption of plasma factor VII in a rabbit model of non-overt disseminated intravascular coagulation.

INTRODUCTION We have recently described an experimental animal model of non-overt disseminated intravascular coagulation (DIC) in the rabbit in which the induction of tissue factor (TF) mRNA and TF antigen expression in peripheral blood leukocytes (PBL) was demonstrated to occur within 2 h of administration of low-dose endotoxin [Hematol. J. 2 (2001) 188]. In the present study, we demonstrate that the leukocyte TF expressed has procoagulant activity leading to a rapid decline in the concentration of factor VII (FVII) in rabbit plasma. METHODS Total plasma FVII antigen and FVIIa were quantitated by rabbit FVII-specific immunoassay and FVIIa-specific clotting assays, respectively. Plasma samples from either saline-injected rabbits or rabbits administered a single bolus of 10 microg/kg Salmonella lipopolysaccharide were compared over a 24-h period. RESULTS Total plasma FVII antigen decreased progressively post-endotoxin injection, reaching 71% of the baseline concentration at 8 h (p<0.001, n=18), and remained low (78%) at 24 h post-injection (p<0.01, n=16), returning to normal by 48 h. Plasma FVIIa levels increased to 120% within 2 h of endotoxin injection, fell to 73% of the baseline concentration at 8 h (p<0.05, n=18) and returned to normal by 24 h post-endotoxin administration. Procoagulant activity of rabbit peripheral blood leukocytes was enhanced at 2 h (p<0.01, n=6) and 4 h (p<0.05, n=6) post-endotoxin injection. The prothrombin time (PT) was increased by <3 s, and thrombin-antithrombin (TAT) complex formation was not significantly increased in the plasma of endotoxin-treated rabbits. No significant changes in total plasma FVII antigen, FVIIa or leukocyte procoagulant activity were observed in rabbits treated with saline. CONCLUSIONS We conclude that the activation of FVII to FVIIa and rapid consumption of total FVII/FVIIa occur very early and likely are integral events linked to the initiation and propagation of non-overt DIC induced by endotoxin.

Mechanism of noncholinergic excitation of canine ileal circular muscle by motilin

In the isolated perfused canine ileal segment, exogenous motilin infused for 9 min, at concentrations from 10(-10) M and 10(-8) M, increased circular muscle motility concomitant with inhibiting tonic VIP release, maximum at 10(-8) M. Both effects increased with increasing motilin concentrations. Atropine 10(-7) M pretreatment did not alter these responses. Naloxone 10(-7) M pretreatment eliminated both the increase in motor activity and the inhibition of VIP levels. Thus the nonmuscarinic neural pathway responsible for motor activation by motilin probably involves the stimulation of release of opiates, which in turn inhibit the release of VIP. Reduction of tonic inhibition of the muscle by continuous VIP release may in part account for increases in motor activity induced by motilin.