Cyclic adenosine 3',5'-monophosphate and leucocyte chemotaxis in vivo.

1 The effect of local elevation of leucocyte cyclic adenosine 3',5'-monophosphate (cyclic AMP) content on the continued migration of leucocytes to a site of acute inflammation was studied in the pleural cavity of rats. 2 Leucocyte cyclic AMP levels were elevated by injecting with the irritant into the pleural cavity dibutyryl cyclic AMP alone or with theophylline. 3 The treatments both produced a marked reduction in leucocyte migration into a pleural reaction induced by immediate hypersensitivity, but had no effect on cell numbers in pleurisy induced either by pyrophosphate or urate crystals.     

Cyclic adenosine 3',5'-monophosphate concentration in rabbit parotid slices following stimulation by secretagotues

The effects of sympathomimetic and parasympathomimetic drugs on cyclic AMP concentration in rabbit parotid slices were investigated. Catecholamines caused a large increase of cyclic AMP which was inhibited by the β-adrenoreceptor blocking agent propranolol; the α-adrenoreceptor blocking agent phentolamine was ineffective. Parasympathomimetic drugs, potent inducers of secretion in vivo and in vitro, did not change the cyclic AMP concentration. These data suggest that the secretory process mediated by cholinergic innervation of the parotid gland is independent of cyclic AMP.     

Effect of sodium ion on levels of cyclic adenosine 3',5'-monophosphate in guinea pig cerebral slices.

Accumulation of cyclic AMP was studied in guinea pig cerebral slices when Na+ levels in the bathing medium were varied or agents which affect tissue Na+ content were added. When NaCl was gradually replaced with Tris-HCl or choline chloride, cyclic AMP formation was progressively enhanced. ;when Na+ was below 30 mM, cyclic AMP formation reached the maximum (approximately 30 fold), but this increment was not blocked by tetrodotoxin. The stimulatory effect of high K+ was nearly linear over 120 mM and became much more prominent when Na+ also was not blocked by tetrodotoxin. Ouabain (10(-4) M), electrical pulses and glutamate (5 x 10(-3) M), each stimulated cyclic AMP formation about 17-, 7- and 5-fold, respectively. Tetrodotoxin (2 x 10(-6) M) completely blocked the effects of electrical pulses and partially blocked the effects of glutamate and oubain. It is suggested that the increase of cyclic AMP in cerebral cortical slices may be related to the decrease in Na+ gradient across the cell membrane.     

The effects of cyclic adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate and theophylline on renin secretion in the isolated perfused kidney of the rat.

1. The influence of cyclic adenosine 3',5'-monophosphate (cyclic AMP), cylic guanosine 3',5'-monophosphate (cyclic GMP) and theophylline on renin secretion was examined in the isolated kidney of the rat perfused with Krebs dextran solution. 2. Neither cyclic AMP (10(-6) to 10(-4) M) nor dibytyryl cyclic AMP (10(-5) M) produced an increase in renin secretion. 3. Cyclic GMP and 8 Br-cyclic GMP caused a small rise in renin secretion in some experiments but this effect was independent of the dose and its physiological significance is uncertain. 4. Theophylline (10(-6) to 10(14) M) caused a significant elevation in renin secretion which was not blocked by (+)-propranolol. Theophylline with cyclic AMP or cyclic GMP did not produce an amplified effect. 5. Despite previous suggestions that cyclic AMP stimulated renin secretion, this could not be confirmed in the present preparation. Since there is no evidence that cyclic AMP or cyclic GMP (or their derivatives, dibutyryl cyclic AMP and 8 Br-cyclic GMP) enter the cells, it will be necessary to study their activity in isolated juxtaglomerular cells to define a possible role.     

Cyclic adenosine 3',5'-monophosphate levels in response to norepinephrine in rectum of postnatal rats.

Age-related changes in cyclic adenosine 3',5'-monophosphate levels in response to norepinephrine (NE) in the rectum of postnatal rats and the localization of cyclic AMP in the rectum were studied. During the first 2 weeks after birth, the basal levels of cyclic AMP were high, NE responses to cyclic AMP contents were minimal and thereafter, the basal cyclic AMP levels rapidly declined, while NE response significantly increased compared to those seen in tissues from adult rats. Furthermore, cyclic AMP immunofluorescence was visualized in smooth muscle and postganglionic neurons of the myenteric plexus. NE application produced an increase of cyclic AMP immunofluorescence in smooth muscle. These results indicate that NE response to cyclic AMP levels in rat rectum is age-dependent and suggest that the majority of beta-adrenoceptors associated with cyclic AMP generating system are localized in the smooth muscle of rat rectum.     

Chemokinesis of rat polymorphonuclear leucocytes and the effect of cyclic adenosine 3',5'-monophosphate.

1 The chemotactic and chemokinetic properties of various substances were studied using rat polymorphonuclear leucocytes (PMN) in Boyden chambers. 2 Casein and the exudate from a carrageenan-induced pleurisy possessed both chemotactic and chemokinetic properties, whereas erythrocyte lysates and albumin showed only chemokinetic activity. 3 Dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP) had little or no effect on the migration towards casein and the inflammatory ecudate, but stimulated the migration towards erythrocyte lysates and albumin. 4 It appears therefore that db cyclic AMP is able to increase a chemokinetic response initiated by other substances. The lack of effect of this compound on cell migration towards substances possessing both chemotactic and chemokinetic properties probably results from the equilibrating effect of a simultaneous stimulation of chemokinesis and inhibition of chemotaxis. 5 These results suggest that studies designed to investigate the effect of anti-inflammatory drugs on cell migration should include the separate assessment of their ability to influence both chemotaxis and chemokinesis.