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PubMed1983

Opioid peptide effects on insulin release and c-AMP in islets of Langerhans.

The time course and specificity of the effect of opioid peptides on c-AMP production in the islets of Langerhans was examined. An enkephalin analogue, d-Ala2Me Phe4 Met(O)-ol enkephalin (DAMME, Sandoz) produced a significant stimulation of basal c-AMP levels, with a peak of stimulation at 5 minutes and a decline thereafter. These changes in intracellular c-AMP levels were of the same order of magnitude as those induced by other secretagogues, but did not coincide in time with the more rapid peak of enkephalin-induced insulin release. The rise in islet c-AMP and insulin secretion induced by DAMME and alpha-endorphin but not leu enkephalin was antagonised by naloxone. The effects of high and low concentrations of a variety of opioid peptides and naloxone on insulin release and islet c-AMP levels were determined, alpha-endorphin, dynorphin, leu enkephalin and met enkephalin all stimulated insulin secretion significantly, though not to the same extent. Higher concentrations of alpha-endorphin, dynorphin and met enkephalin inhibited insulin release relative to effects at low opiate concentrations. However, higher concentrations of leu enkephalin stimulated insulin release further. We conclude from these results that the mode of action of opioid peptides in stimulating insulin release is not via increased islet c-AMP exclusively. Furthermore, the results obtained with different classes of opioid suggest the presence of distinctive types of opiate receptor in islets of Langerhans.

Animals↗
PubMed1990

Adenine nucleotide depletion in human muscle during exercise: causality and significance of AMP deamination.

The predominant route for adenine nucleotide catabolism in skeletal muscle is deamination of AMP to inosine monophosphate (IMP) and ammonia (NH3). Deamination of AMP is enhanced during exercise when the capacity to rephosphorylate ADP is impaired. Thus, in human muscle the formation of IMP (NH3) during exercise is augmented under the following conditions (1) at high intensities, (2) during beta-adrenoceptor blockade, (3) during hypoxia, (4) after detraining, and (5) at low glycogen levels. The formation of IMP is related to the metabolic stress (as indicated by the degree of phosphocreatine breakdown and lactate accumulation), the rate of ATP turnover, and the fiber type composition. During maximal exercise at 100% of VO2max or sustained isometric contractions to fatigue, about 15% of the adenine nucleotide (AN) pool is degraded through deamination of AMP to IMP. It is suggested that the stimulus for increased AMP deamination is increased transient levels of ADP and AMP in the contracting muscle fiber. Deamination of AMP to IMP and NH3 provides a sink for ADP, whereby the ATP/ADP ratio and the phosphorylation potential are kept high, which may be essential for the continuation of the contraction process. This implies that the relative levels of the adenine nucleotides are more important for maintenance of adequate cellular function than the absolute concentration of ATP.

AMP Deaminase↗
PubMed1986

AMP deaminase activity of skeletal muscle in neuromuscular disorders in childhood. Histochemical and biochemical studies.

We studied the histochemical staining and biochemical activity of AMP deaminase in biopsied muscle in Becker-type muscular dystrophy (BMD), Fukuyama-type congenital muscular dystrophy (FCMD), Duchenne-type muscular dystrophy (DMD), Werdnig-Hoffmann disease (WH) in order to elucidate the change of AMP deaminase activity in muscle with neuromuscular disorders in childhood. The intensity of AMP deaminase staining did not decrease in BMD with mild pathologic change, but in DMD, FCMD and WH it decreased in parallel with the severity of the pathologic change. The biochemical activity of AMP deaminase did not decrease in muscle with mild pathologic change in patients with DMD and tended to decrease according to the progress of the disease. The activity of AMP deaminase in muscle of patients with FCMD and WH which showed severe pathologic change was remarkably low. It was demonstrated that the decrease in the activity of AMP deaminase was related to the intensity of pathologic change rather than diagnosis of a neuromuscular disorder.

AMP Deaminase↗
PubMed1969

Evidence for a role of cyclic AMP in neuromuscular transmission.

Experiments were undertaken to determine if the effects of epinephrine in promoting neuromuscular transmission were mediated by adenosine 3':5'-cyclic phosphate (cyclic AMP). Dibutyryl cyclic AMP and the methyl xanthines, theophylline and caffeine (which inhibit cyclic AMP hydrolysis), were found to increase the amplitude of the end plate potential in the isolated rat diaphragm. Like epinephrine (which is known to promote cyclic AMP synthesis), these agents appear to facilitate the release of acetylcholine from the motor neuron. This interpretation is supported by the observation that theophylline and dibutyryl cyclic AMP markedly increased the frequency but not the amplitude of the spontaneous miniature end plate potentials. In addition, these drugs increased the number of transmitter packets released in response to nerve stimulation. These results are consistent with the view that cyclic AMP plays a role in the release of acetylcholine and in the "defatiguing effect" of epinephrine.

Acetylcholine↗
PubMed1970

Cyclic AMP receptor protein of E. coli: its role in the synthesis of inducible enzymes.

A cyclic AMP binding protein has been purified over 100-fold from E. coli extracts. Protein purified from wild-type strains binds cyclic AMP with an apparent dissociation constant of 1-2 x 10(-6)M. Two mutant strains that are unresponsive to exogenous cyclic AMP have altered binding activity; the protein purified from one of these mutants has a decreased affinity for cyclic AMP (apparent dissociation constant = 2 x 10(-5)M). Extracts of this mutant are deficient in their ability to support beta-galactosidase synthesis in vitro. The addition of purified, wild-type binding protein to these extracts restores enzyme synthesis toward normal. Because this binding protein appears to be required for cyclic AMP action, we suggest it be called the cyclic AMP receptor protein (CR protein).

Adenine Nucleotides↗
PubMed1975

Cyclic AMP-dependent endogenous phosphorylation of a microtubule-associated protein.

Microtubules prepared from chick brain homogenates by successive cycles of assembly-disassembly were found to contain two high-molecular-weight proteins, designated microtubule-associated protein1 and microtubule-associated protein2. Microtubule-associated protein2 (apparent molecular weight 300,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) was the preferred substrate for an endogenous cyclic AMP-dependent protein kinase which appeared to be an integral component of the microtubules. The initial rate of phosphorylation of microtubule-associated protein2 was enhanced 4- to 6-fold by cyclic AMP, with half-maximal stimulation occurring at 2 times 10-7 M cyclic AMP. Under optimal conditions, a total of 1.0 and 1.9 mol of phosphate was incorporated per mole of microtubule-associated protein2, in the absence and presence of cyclic AMP, respectively. Cyclic AMP also stimulated the phosphorylation of tubulin, but the rate of phosphate incorporation per mol of tubulin was only 0.15% that of microtubule-associated protein2. The data raise the possibility that the cyclic AMP-dependent phosphorylation of microtubule-associated protein 2 may play a role in microtubule assembly or function.

Animals↗
PubMed1976

Effect of 3':5'-cyclic AMP on glucose transport in rat adipocytes.

An indirect method for obtaining a reliable measure of the rate of glucose transport into adipocytes is described. Evidence is presented that altered levels of 3':5'-cyclic AMP can influence the transport of glucose into adipocytes. When cyclic AMP levels were lowered with antilipolytic agents (insulin, nicotinic acid, or clofibrate), rates of glucose transport were increased. In contrast, when adipose tissue levels of cyclic AMP were elevated by lipolytic hormones or theophylline, glucose transport when cyclic AMP levels were elevated by lipolytic agents. Agents that can raise cyclic AMP but inhibit lipolytic (procaine, amitryptyline, and phenylethylbiguanide) reduced the rate of glucose transport. Other data are presented that are consistent with the conclusion that cyclic AMP inhibits glucose transport into adipocytes.

Adipose Tissue↗
PubMed1977

Effects of colchicine on cyclic AMP levels in human leukocytes.

The increase in human leukocyte adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels seen in response to various substances was markedly potentiated by colchicine and other agents that affect microtubule assembly. Addition of dl-isoproterenol (2 muM) or prostaglandin E(1) (10 muM), together with the phosphodiesterase inhibitor isobutylmethylxanthine (1 mM), caused a much greater increase in cyclic AMP in colchicine-pretreated cells than in control cells. With isoproterenol (2 muM) plus isobutylmethylaxanthine (1 mM), cyclic AMP levels rose about 3-fold but, in combination with colchicine, these drugs caused a more than 15-fold increase in cyclic AMP. The effects of colchicine were both time- and dose-dependent; they could be seen within 1 min after addition of colchicine or at concentrations as low as 10 nM. In addition to its potentiation of hormonally induced increases in cyclic AMP levels, colchicine also potentiated the effect of isobutylmethylxanthine alone on leukocyte cyclic AMP levels. Vinblastine, vincristine, podophyllotoxin, and oncodazole all had effects similar to those of colchicine but lumicolchicine did not. The data suggest that cytoplasmic microtubules interact with the leukocyte plasma membrane to impose constraints on the expression of hormone-sensitive adenylate cyclase; the therapeutic effects of colchicine may depend in part upon the relaxation of such constraints. Moreover, the synergism described here between colchicine-like agents and hormones is of potential therapeutic importance in clinical conditions in which either alkaloid or hormone has been useful separately.

Colchicine↗
PubMed2005

Does AMP-activated protein kinase couple inhibition of mitochondrial oxidative phosphorylation by hypoxia to calcium signaling in O2-sensing cells?

Specialized O2-sensing cells exhibit a particularly low threshold to regulation by O2 supply and function to maintain arterial pO2 within physiological limits. For example, hypoxic pulmonary vasoconstriction optimizes ventilation-perfusion matching in the lung, whereas carotid body excitation elicits corrective cardio-respiratory reflexes. It is generally accepted that relatively mild hypoxia inhibits mitochondrial oxidative phosphorylation in O2-sensing cells, thereby mediating, in part, cell activation. However, the mechanism by which this process couples to Ca2+ signaling mechanisms remains elusive, and investigation of previous hypotheses has generated contrary data and failed to unite the field. We propose that a rise in the cellular AMP/ATP ratio activates AMP-activated protein kinase and thereby evokes Ca2+ signals in O2-sensing cells. Co-immunoprecipitation identified three possible AMP-activated protein kinase subunit isoform combinations in pulmonary arterial myocytes, with alpha1 beta2 gamma1 predominant. Furthermore, their tissue-specific distribution suggested that the AMP-activated protein kinase-alpha1 catalytic isoform may contribute, via amplification of the metabolic signal, to the pulmonary selectivity required for hypoxic pulmonary vasoconstriction. Immunocytochemistry showed AMP-activated protein kinase-alpha1 to be located throughout the cytoplasm of pulmonary arterial myocytes. In contrast, it was targeted to the plasma membrane in carotid body glomus cells. Consistent with these observations and the effects of hypoxia, stimulation of AMP-activated protein kinase by phenformin or 5-aminoimidazole-4-carboxamide-riboside elicited discrete Ca2+ signaling mechanisms in each cell type, namely cyclic ADP-ribose-dependent Ca2+ mobilization from the sarcoplasmic reticulum via ryanodine receptors in pulmonary arterial myocytes and transmembrane Ca2+ influx into carotid body glomus cells. Thus, metabolic sensing by AMP-activated protein kinase may mediate chemotransduction by hypoxia.

AMP-Activated Protein Kinases↗
PubMed1979

Role of cyclic AMP in glucagon-induced stimulation of hepatic glucose output in man.

The interrelationship between glucagon action on splanchnic glucose output and cyclic AMP production was studied in healthy volunteers after hepatic venous catheterization. Glucagon was infused according to four different protocols to achieve arterial levels ranging from 300 to 9000 ng/l. Infusion of glucagon which resulted in arterial levels of the hormone of 4000-9000 ng/l was associated with a marked increase in net splanchnic cyclic AMP production and in the arterial levels of the cyclic nucleotide. The rise in cyclic AMP efflux from the splanchnic area was transient but an augmented splanchnic production was still evident after 30 min of glucagon infusion. Splanchnic glucose output rose 3-5 fold. Infusion of glucagon at lower rates, resulting in arterial levels of 300-900 ng/l, did not measureably stimulate the efflux of cyclic AMP from the splanchnic area. In spite of this, splanchnic glucose output rose 2-3 fold and the blood glucose level increased 20-50% during glucagon infusion at these lower rates. It is concluded that (1) factors other than cyclic AMP are rate limiting in the stimulation of hepatic glucose production, and (2) although cyclic AMP is an established 'second messenger' of glucagon action, other factors may also be of importance in mediating the physiological response of this hormone.

Adult↗
PubMed1979

Regulation of secretion of parathormone and secretory protein-I from separate intracellular pools by calcium, dibutyryl cyclic AMP, and (1)-isoproterenol.

Dispersed porcine parathyroid cells were incubated at calcium concentrations between 0.5 and 3.0 mM in the presence of 3H- or 14C-amino acids to label newly synthesized parathormone. Up to four times more hormone was secreted at the lower calcium concentration but its specific radioactivity, from 30 to 50 times that of the intracellular pool, did not change. Dibutyrl cyclic AMP doubled immunoactive parathormone secretion at each calcium concentration, but there was no increase in secretion of radioactive hormone if labeled amino acids and secretagogue were added simultaneously. Similarly, when the intracellular pool of parathormone was prelabeled with 3H-amino acids and then the cells were incubated in 14C-amino acids and dibutyryl cyclic AMP, the entire increase in hormone secreted was derived from the prelabeled pool. (1)-isoproterenol increased intracellular cyclic AMP and acted on hormone secretion in a manner indistinguishable from dibutyryl cyclic AMP. In similar double-label experiments dibutyryl cyclic AMP preferentially enhanced secretion of secretory protein-I, a calcium-regulated protein of the parathyroid of unknown function. Calcium, alone, inhibited the intracellular level of cyclic AMP in a concentration-dependent fashion. These data are consistent with the existence in the parathyroid cell preparation of two hormone and secretory protein pools that may be individually recruitable--one consisting of most recently synthesized protein, the other consisting of older "storage" protein. The data do not allow one to decide whether the two pools coexist within individual cells or whether, instead, they exist in separate cells of the dispersed gland preparation.

Animals↗
PubMed1994

Milrinone, a cyclic AMP-phosphodiesterase inhibitor, has differential effects on regional myocardial work and oxygen consumption in experimental left ventricular hypertrophy.

OBJECTIVE: The aim was to test the hypothesis that local myocardial work and O2 consumption would respond differentially to milrinone, a selective cyclic AMP-phosphodiesterase inhibitor, in left ventricular hypertrophy due to differences in myocardial cyclic AMP-phosphodiesterase activity. METHODS: The effect of milrinone on regional segment work and regional O2 consumption was measured in 12 open chest anaesthetised dogs with left ventricular hypertrophy induced by valvular aortic stenosis and in 10 age matched control dogs. Regional myocardial work was calculated as the integrated product of instantaneous force development (miniature transducer) and segment shortening (sonomicrometer). Regional O2 consumption was calculated from coronary blood flow (radiolabelled microspheres) and O2 saturations in small regional vessels (microspectrophotometry). Low Km phosphodiesterase activity was assayed by measuring the hydrolysis of radiolabelled cyclic AMP. RESULTS: Milrinone increased left ventricular dP/dtmax by approximately 60-70% in both control [2808(SEM 314) to 4584(660) mm Hg.s-1] and left ventricular hypertrophy [3279(258) to 5589(470) mm-Hg.s-1]. Regional work increased significantly in control [612(88) to 955(101) g.mm.min-1], while the increase was not significant in left ventricular hypertrophy [859(139) to 974(172) g.mm.min-1]. Regional O2 consumption increased significantly with milrinone in left ventricular hypertrophy [8.1(1.2) to 13.1(2.4) ml O2.min-1.100 g-1], but the increase was not significant in control [6.9(1.2) to 7.4(1.0) ml O2.min-1.100 g-1]. Myocardial stiffness during ejection was increased by milrinone to a significantly greater extent in animals with left ventricular hypertrophy. These effects were not related to differences in cyclic AMP-phosphodiesterase activity between control hearts and hearts with left ventricular hypertrophy [393(45) v 402(36) pmol.mg protein-1.1]. CONCLUSIONS: Differences between the hypertrophied and normal canine myocardium in response to milrinone are either due to altered levels of cyclic AMP production in left ventricular hypertrophy, to effects of milrinone that are unrelated to cyclic AMP-phosphodiesterase inhibition, or to other differences in hypertrophied hearts. The greater stiffness of the myocardium in left ventricular hypertrophy may require a greater energy expenditure to increase the amount of work it performs.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1981

Physiological effects of caffeine in the rat: extracellular cyclic AMP status, growth pattern and glucose metabolism in adipose tissue.

The authors investigated the effect of moderate caffeine intake on overall cyclic adenosine monophosphate (AMP) metabolism in the rat and its relationship to growth and glucose metabolism in adipose tissue. Male Sprague-Dawley weanling rats were divided into control and treatment groups. The latter received caffeine via drinking water (0.06 mg/ml H2O) during a 4-week period whereas controls received water only. At weekly intervals, urinary cyclic AMP excretion, food intake and weight gain were measured. Plasma cyclic AMP caffeine and glucose were determined at moment of death and in vitro lipogenesis and glycogen synthesis from [6-14C]glucose in epididymal adipose tissue were assayed. Although urinary cyclic AMP excretion was negatively correlated to caffeine intake during the 2nd week of the experiment, this did not reach significant levels, nor did this trend continue into the 4th week. Growth pattern and food efficiency were similar in both groups as were blood glucose and cyclic AMP values at moment of death. In vitro glycogen synthesis from [6-14C] glucose in adipose tissue showed a 40% increase, this parameter being positively correlated with plasma caffeine concentration. Glucose uptake and lipogenesis were unaltered in epididymal fat pads. These data suggest that regular intake of a moderate dose of caffeine leads to homeostasis of overall cyclic AMP metabolism and of selected physiological parameters under study. Alteration of glycogen synthesis in adipose tissue is discussed in relation to documented effects of caffeine ingestion on catecholamine secretion.

Adipose Tissue↗
PubMed1994

Effects of a novel cardiotonic agent (+-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-quinolino ne (OPC-18790) on contractile force, cyclic AMP level, and aequorin light transients in dog ventricular myocardium.

We studied the effects of a novel cardiotonic agent OPC-18790 [(+-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)- quinolinone] on isometric contractions, intracellular aequorin light transients, and cyclic AMP levels in isolated dog ventricular trabeculae. The positive inotropic effect (PIE) of OPC-18790 (1-30 microM) was consistently associated with an abbreviation of contractions and an increase in the amplitude of aequorin light transients. The maximum responses of Ca2+ transients and force to OPC-18790 were approximately 40% of the isoproterenol-induced maximum. Carbachol (3 microM) markedly attenuated the increases in force, light transients, and cyclic AMP accumulation induced by OPC-18790. These results indicate that OPC-18790 is a cardiotonic agent with moderate effectiveness, and that the PIE of OPC-18790 may be produced mainly by an increase in intracellular Ca2+ transients induced by cyclic AMP accumulation. For a given increase in amplitude of Ca2+ transients, OPC-18790 produced a more pronounced increase in force of contraction (FOC) than did isoproterenol, suggesting that OPC-18790 does not produce as great a decrease in Ca2+ sensitivity of contractile proteins as does isoproterenol. These observations indicate that among cardiotonic agents acting through cyclic AMP pathway, regulation of contractility produced by the selective cyclic AMP phosphodiesterase III (PDE-III) inhibitor OPC-18790 is qualitatively different from the regulation induced by isoproterenol that acts on cyclic AMP generation in intact myocardial cells.

Aequorin↗
PubMed1977

Hypocalcemia and nephrogenous cyclic AMP production in critically ill or injured patients.

Critically ill or injured patients often have impaired cardiovascular function. Since low ionized calcium levels can cause such changes, serum calcium and urine calcium were measured in a prospective study involving 28 criticially ill or injured patients and 16 normal controls. Serum protein levels were also measured to calculate "corrected" total calcium levels. Ionized calcium levels are difficult to measure. Since ionic hypocalcemia is thought to increase the "nephrogenous production" of cyclic AMP, cyclic AMP levels were measured in the blood and urine of these patients and the "nephrogenous" cyclic AMP calculated from the creatinine clearance. The mean total serum calcium in these patients was 7.7 +/- 0.8 mg/dl (S.D.). This was significantly lower (p less than 0.001) than our controls (9.6 +/- 0.6). When corrected for hypoproteinemia, the mean serum calcium (8.7 +/- 0.8) was still significantly lower (p less than 0.005) than control (9.4 +/- 0.5). The mean urine calcium excretion in the patients (56 +/- 66 mg/100 ml G.F.R.) was lower, but not significantly so, than in the controls (84 +/- 44 mg/100 ml G.F.R.). The "apparent nephrogenous" cyclic AMP in the study group was 2,731 +/1 1,451 pm/ml/100 ml G.F.R. The nephrogenous cyclic AMP had a negative correlation (r =-0.45) with "corrected" total calcium levels. Thus "total," "corrected" total, and "ionized" calcium levels appear to be reduced in the majority of critically ill or injured patients studied. The clinical implications of these findings and the potential value of serial cyclic AMP determinations in blood and urine will be discussed.

Blood Proteins↗
PubMed2001

The role of cyclic AMP in the pathogenesis of glucose desensitization in rat pancreatic islets.

Adenosine-3',5'-cyclic monophosphate (cyclic AMP) promotes exocytosis of insulin in pancreatic beta cells. This study was performed to investigate the role of cyclic AMP in the pathogenesis of glucose desensitization in rat pancreatic islets. In islets cultured with high glucose for 48 hours, 27 mmol/L glucose-induced insulin release was markedly impaired, while 3.3 mmol/L glucose-or arginine-induced insulin release was enhanced, indicating glucose desensitization. Islet cyclic AMP content was 190% enhanced in high glucose-culture islets for 48 hours. In islets cultured with dibutyryl-cyclic AMP (dbcAMP) or 3-isobutyl methy-xanthine (IBMX), islet insulin content or 27 mmol/L glucose-induced insulin release was deteriorated. In contrast, 3.3 mmol/L glucose- or arginine-induced insulin release was increased, which was similar to glucose-desensitized islets. Wash-out of dbc AMP for the last 24 hours of the 48-hour culture period restored impaired high glucose-induced insulin release in the same manner as wash-out of high glucose. Diazoxide, the KATP channel opener, also restored impaired high glucose-induced insulin release from dbcAMP-cultured islets. The data suggest that enhancement of cyclic AMP in high glucose-culture islets may be one of the pathogenesis of glucose desensitization.

1-Methyl-3-isobutylxanthine↗
PubMed1975

Reduced epidermal cyclic AMP accumulation following prostaglandin stimulation: Its possible role in the pathophysiology of psoriasis.

Since prostaglandins are known to be one of the modulators of cyclic AMP, a study of the role of prostaglandins and their relation to the regulation of the nucleotide in psoriasis was initiated. Guinea-pig epidermal preparations were incubated with prostaglandins (PGs) in the presence of theophylline. PGE1 increased cyclic AMP levels 3.5-fold whereas a 2-fold increase was seen with PGE2 and PGA1. The increase in cyclic AMP accumulation was linear with increasing concentration of PGE1, from 10(-11) to 10(-5) M. PGE1 significantly increased cyclic AMP in psoriatic epidermis in vitro; however, the stimulation of cyclic AMP accumulation was significantly less in involved epidermis as compared with uninvolved tissue. The specificity of this stimulation, its occurrence at physiologic levels, and the decreased responsiveness of the cyclic AMP system in psoriatic epidermis to PGE1 stimulation suggest that the altered response of epidermis to PGs may be one of the factors in the pathophysiology of psoriasis.

Animals↗
PubMed1984

Comparison between the effects of inhaled isoprenaline and fenoterol on plasma cyclic AMP and heart rate in normal subjects.

The time course of changes in plasma cyclic AMP, heart rate and bronchial tone after inhalation of fenoterol or isoprenaline from a dose-metered aerosol are reported in a group of normal subjects. After isoprenaline, plasma cyclic AMP increased rapidly reaching a peak by 10 min and returned to basal levels within 60 min. A rapid, transient rise in heart rate occurred that was maximal by 5 min and returned to a basal level by 45 min. After fenoterol, the changes in cyclic AMP and heart rate were of much longer duration. The rise in plasma cyclic AMP was slower in onset and of greater magnitude than for isoprenaline, reaching a peak by 20 min and remaining above basal level for more than 6 h. The maximum increase in heart rate after fenoterol was less than that observed with isoprenaline but an elevated rate persisted for 4 h after inhalation of fenoterol. Fenoterol is known to have a longer duration of action as a bronchodilator in comparison with isoprenaline. The prolonged rise in plasma cyclic AMP in normal subjects given inhaled fenoterol may reflect this long duration of action. The concomitant rise in heart rate, however, suggests that the duration of plasma cyclic AMP response may in part be due to the systemic effect of the fraction of inhaled fenoterol known to be absorbed via the buccal and intestinal routes.

Absorption↗