Mechanism of effect of dibutyryl cyclic adenosine 3',5'‐monophosphate on canine renal renin release.

Abstract

SUMMARY1. We evaluated the effect of intrarenal arterial infusion of dibutyryl cyclic AMP on renal renin release.2. Dibutyryl cyclic AMP (300 gg/kg. min) produced significant and reversible increases in renin secretion rate, renal blood flow and urinary Na+ excretion.3. In the non-filtering kidneys, dibutyryl cyclic AMP increased renin secretion rate and renal blood flow.4. In indomethacin-treated dogs, dibutyryl cyclic AMP also produced significant and reversible increases in renin secretion rate and renal blood flow but had no effect on Na+ excretion.5. During infusion of dibutyryl cyclic AMP, infusion of the Ca ionophore A23187 failed to inhibit renin release.6. These findings suggest that the effect of dibutyryl cyclic AMP on renin release is not mediated by prostaglandins or intracellular Ca and does not involve the macula densa.7. We conclude that dibutyryl cyclic AMP has a direct effect on the juxtaglomerular cells.

Forskolin and calcium: interactions in the control of renin secretion and perfusate flow in the isolated rat kidney.

“…In an attempt to determine which of these two cellular signals play a possible primary role, Churchill & Churchill (1982) (Vandongen & Peart, 1974;Churchill & Churchill, 1982;Schwertschlag & Hackenthal, 1982;Knepel, Reimann & Nutto, 1982). Bondar et al (1984) The data presented here are in general agreement with the view of Churchill & Churchill (1982) that Ca2+ is a final common pathway whereby extracellular events are coupled to renin secretion; the results also agree with the recently advanced hypothesis that Ca2+ permeability of the juxtaglomerular cell membrane is of central importance in the mechanisms controlling renin secretion (Fray et al 1983b). Since renal perfusate flow may also be monitored in this preparation, the interaction between cyclic AMP and Ca2+ in the control of flow has been examined and discussed in the context of a recently published hypothesis on the role of Ca2+ in the control of renal blood flow .…”

“…These observations and the general conclusion that raising intracellular Ca2+ blocks the renin secretary response induced by cyclic AMP-mediated agents (or by an analogue of cyclic AMP) are in agreement with several reports (Vandongen & Peart, 1974;Logan & Chatzilias, 1980;Churchill & Churchill, 1982;Knepel et al 1982; Kurtz et al 1984). They disagree with the conclusions of a recently published study showing that cyclic AMP-mediated renin secretion is unaffected by A23187, the Ca2+ ionophore which is believed to raise cellular Ca2+ (Bondar et al 1984). An obvious explanation for the discrepancy may be that the concentration of A23187 used in the study of Bondar et al (1984) (Rinaldi, Capony & Demaille, 1982;Reuter, 1983;Bean, Nowycky & Tsien, 1984;Cachelin, de Peyer, Kokubum & Reuter, 1983;Siegelbaum & Tsien, 1983;Mauger, Poggioli, Guesdon & Claret, 1984).…”

“…They disagree with the conclusions of a recently published study showing that cyclic AMP-mediated renin secretion is unaffected by A23187, the Ca2+ ionophore which is believed to raise cellular Ca2+ (Bondar et al 1984). An obvious explanation for the discrepancy may be that the concentration of A23187 used in the study of Bondar et al (1984) (Rinaldi, Capony & Demaille, 1982;Reuter, 1983;Bean, Nowycky & Tsien, 1984;Cachelin, de Peyer, Kokubum & Reuter, 1983;Siegelbaum & Tsien, 1983;Mauger, Poggioli, Guesdon & Claret, 1984). Recent evidence has also suggested another mechanism whereby forskolin (and thereby cyclic AMP) may stimulate renin secretion.…”

“…An abundant amount of evidence suggests that cyclic AMP stimulates whereas Ca2+ inhibits renin secretion (Peart, 1977;Fray, 1977;Harada & Rubin, 1978;Park & Malvin, 1978;Park, Han & Fray, 1981;Churchill & Churchill, 1982;Naftilan & Oparil, 1982;Ginesi, Munday & Noble, 1983;Fray, Lush & Valentine, 1983b;Hackenthal, Schwertschlag & Taugner, 1983;Kurtz, Pfeilschifter & Bauer, 1984; Fray O'Dea, Hansen & Mirkin, 1984; Bondar, Cadnapaphornchai, McDonald & Taher, 1984). In an attempt to determine which of these two cellular signals play a possible primary role, Churchill & Churchill (1982) (Vandongen & Peart, 1974;Churchill & Churchill, 1982;Schwertschlag & Hackenthal, 1982;Knepel, Reimann & Nutto, 1982).…”