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Biomedical subjects

J A Ferrendelli

Publications and source records attributed to J A Ferrendelli.

At least 127 records · Page 7Linked to original sources
PubMed1976

Cellular depolarization and cyclic nucleotide content in central nervous system.

There is ample evidence indicating that cAMP and cGMP content in mamalian brain is markedly influenced by cellular depolarization. The relationships between the two cyclic nucleotides and the complex process of cellular depolarization, which in turn leads to extensive functional and metabolic consequences are incompletely understood, however. Much data, which are reviewed in the present chapter, suggest that cellular depolarization leads to elevation of cAMP and cGMP levels by two different and unrelated mechanisms. With regard to cAMP, it seems reasonable to conclude that cellular depolarization in CNS causes a release of adenosine, and it is the subsequent action of this substance which accounts for a portion of the elevation of cAMP levels. At present, one cannot ascertain whether or not other factors contribute to the increase of cAMP content resulting from cellular depolarization. It is probable that it is not cellular depolarization, per se, but the influx of Ca2+ into intracellular spaces caused by cellular depolarization which increases the content of cGMP. The specific effects of Ca2+, Mg2+, and other divalent cations on the cGMP response suggest a close relationship between the cyclic nucleotide and some process associated with release of one or more yet undefined neurotransmitters. Wether the involvement is in presynaptic or postsynaptic mechanisms also remains to be determined.

Animals↗
PubMed1975

The role of Ca-2+ and cyclic adenosine 3':5'-monophosphate in insulin release induced in vitro by the divalent cation ionophore A23187.

Insulin release from isolated perifused pancreatic islets was stimulated by the divalent ionophore A23187 in the absence of exogenous glucose. In addition, A23187 produced a 2-fold elevation of cyclic adenosine 3':5'-monophosphate (cAMP) levels in isolated perifused islets. The elevation of cAMP levels coincided with peak insulin release. Ionophore-induced insulin release was unaffected by pretreatment of the islets with theophylline (5 mM). Stimulation of insulin release produced by the ionophore occurred either in the presence or absence of extracellular Ca-2+; however, cAMP accumulation required the presence of extracellular Ca-2+. The ionophore (10 muM) had no effect on adenylate cyclase activity of homogenates of isolated islets. The results of this study are interpreted as indicating that intracellular Ca-2+ has an essential role in the insulin releasing mechanism, whereas the cAMP system has a modulatory effect on this process.

Animals↗
PubMed1975

Comparison of the effects of biogenic amines on cyclic GMP and cycle AMP levels in mouse cerebellum in vitro.

Norepinephrine (NE) elevates levels of both 3',5'-guanosine monophosphate (cyclic GMP) and 3',5'-adenosine monophosphate (cyclic AMP) in incubated slices of mouse cerebellum. As little as 1 muM NE is capable of increasing the level of either cyclic nucleotide. Maximal elevations of cyclic AMP and cyclic GMP levels produced by NE are 15- to 40-fold and 2- to 4-fold, respectively. Dopamine, serotonin and histamine, other biogenic amines considered to be neurotransmitters in CNS, have no effect on mouse cerebellum cyclic nucleotide levels except at relatively high (1 mM) concentrations. NE-induced accumulation of cyclic GMP, but not cyclic AMP, is blocked by omission of Ca2+ from the incubation media. Theophylline does not alter the effect of this catecholamine on either cyclic nucleotide. In tissue slices incubated in buffered sucrose or in choline-Krebs buffer, NE is still capable of increasing both cyclic GMP and cyclic AMP levels; however, these elevations are less than those observed in brain slices incubated in Krebs-Ringer buffer. NE, in combination with glutamate, produces supra-additive elevations of both cyclic GMP and cyclic AMP levels. However, NE in combination with adenosine or high levels of K+ only has a synergistic effect on cyclic AMP and not on cyclic AMP and not on cyclic GMP combination. The elevation of cyclic AMP levels produced by NE appears to be mediated via both alpha- and beta-adrenergic receptor sites. In contrast, the receptor site(s) mediating cyclic AMP accumulation do not appear to be either typical alpha- or beta-adrenergic receptors.

Adenosine↗
PubMed1975

Factors governing glucose induced elevation of cyclic 3'5' AMP levels in pancreatic islets.

Adenosine 3'5'-cyclic monophosphate (cAMP) levels of isolated perifused pancreatic islets were elevated by high levels of glucose concomitantly with initiation of enhanced insulin secretion. The rise of cAMP was biphasic and seemed to be related to the temporal biphasic kinetics of insulin release. However, the temporal profiles of cAMP level changes and of insulin release differed; the major rise of the cAMP levels was seen during the initial phase, whereas insulin secretion was more pronounced during the second phase of release. Glucose-induced cAMP elevation required the presence of extracellular Ca++. Mannoheptulose completely blocked cAMP elevation due to high glucose. Exogenous insulin which has been shown by others to inhibit insulin secretion in vitro, blunted the glucose-induced cAMP rise. These observations and data in the literature are compatible with the concept that under physiological conditions glucose governs the intracellular cAMP levels in a Ca++ dependent manner - either directly or indirectly through metabolic effects.

Animals↗
PubMed1973

Mechanism of action of nerve growth factor and cyclic AMP on neurite outgrowth in embryonic chick sensory ganglia: demonstration of independent pathways of stimulation.

The suggested role of adenosine 3':5'-cyclic monophosphate as the "second messenger" in the neurite outgrowth from chick embryonic sensory ganglia mediated by nerve growth factor was examined. Although N(6),O(2)-dibutyryl adenosine 3':5'-cyclic monophosphate induces fiber outgrowth at concentrations of 1-5 mM, this response is morphologically distinct from that produced by nerve growth factor, is pH dependent, is mimicked by sodium butyrate, and does not occur in sympathetic ganglia. In addition, nerve growth factor does not alter the amounts of intracellular cyclic AMP during incubations up to 24 hr and does not stimulate adenylate cyclase in broken-cell preparations. Addition of theophylline, an inhibitor of phosphodiesterase, causes increases in intracellular levels of cyclic AMP but does not affect fiber outgrowth. These observations indicate that the nerve growth factor response is not mediated through cyclic AMp and that stimulation of sensory ganglia by exogenous cyclic AMP derivatives is probably of limited physiological significance. These findings are also compatible with the developing hypothesis, based on structural similarities, that nerve growth factor and insulin exert their effects on their respective responsive tissues by related mechanisms.

Adenylyl Cyclases↗