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Biomedical subjects

J B Osnes

Publications and source records attributed to J B Osnes.

At least 73 records · Page 4Linked to original sources

Competitive blockade of alpha-adrenergic receptors in rat heart by prazosin.

Phenylephrine (PE) in presence of propranolol evokes an alpha-adrenergic inotropic response in rat heart. The time course of this response is characterized by a transient decrease in maximal developed tension (Tmax) to subcontrol levels (negative phase of the inotropic response) followed by an increase which reaches maximum after 4-5 min. (positive phase of the inotropic response). Prazosin (PRZ), a selective alpha 1-receptor blocker, inhibited preferentially the positive phase of the inotropic response and displaced the dose-response curve of PE to the right in nanomolar concentrations, indicating a competitive mechanism of inhibition. Phentolamine, a non-selective alpha-blocker, blocked both the negative and the positive phase of the inotropic response to about the same degree. PRZ appears to be a competitive alpha-adrenergic antagonist with high affinity in rat heart. Two populations of alpha-adrenergic receptors may be present: one stimulatory (alpha 1) and one inhibitory.

Adrenergic alpha-Antagonists↗

A radioimmunoassay for cyclic AMP (cAMP) obtained by acetylation of both unlabeled and labeled (3H-cAMP) ligand, or of unlabeled ligand only.

A sensitive radioimmunoassay (limit of detection 7 +/- 1 fmol per tube) for cyclic AMP (cAMP) based on acetylation of both 3H-cAMP and unlabeled ligand was developed. Rabbit anti-cAMP antibodies had an apparent Ka for the acetylated ligand of 2 x 10(10) l/mol. When the unlabeled ligand only was acetylated an increased sensitivity was obtained without loss of specificity.

Acetylation↗

Qualitative differences between beta-adrenergic and alpha-adrenergic inotropic effects in rat heart muscle.

If beta- and alpha-adrenergic inotropic effects are cyclic AMP dependent and cyclic AMP independent, respectively, they may be qualitatively different. The inotropic effects of beta-receptor stimulation (isoprenaline) and alpha-receptor stimulation (phenylephrine combined with propranolol) were characterized in isolated perfused rat hearts, rat atria and rat papillary muscles. The beta-effect reached its maximum before the alpha-effect. The alpha-effect followed a three-phasic time-course indicating both stimulatory and inhibitory components. The aortic pressure wave (perfused heart) indicated a shorter contraction phase after beta-stimulation than after alpha-stimulation. The time to peak tension (atrium, papillary muscle) was relatively shorter after isoprenaline than after alpha-stimulation, which tended to prolong it. The contraction-relaxation cycles (atrium, papillary muscle) were examined by recording the isometric tension (T), its first (T') and second (T'') deri derivatives. alpha and beta-stimulation both increased Tmax, T'max (maximal rate of tension rise), T'min (maximal rate of tension decline) and T''min (maximal rate of transition from rise to decline of tension). Isoprenaline increased T'min (papillary muscle) and T''min (atrium, papillary muscle) relatively more than did alpha-stimulation, i.e. the relaxing processes were activated relatively more by beta-stimulation. The results indicate different mechanisms for the two adrenergic inotropic effects. The relatively larger activation of relaxation by beta-stimulation is assumed to be caused by clic AMP.

Adrenergic alpha-Agonists↗

Cyclic AMP formation and morphology of myocardial cells isolated from adult heart: effect of Ca2+ and Mg2+.

Adult rat heart cells were isolated by perfusion with a calcium-free phosphate buffer containing collagenase. Optimal conditions gave a high proportion of elongated cells. Isoprenaline increased cydic AMP content linearly, with ED50 (dose effective in 50% of the population) about 10(-7) M. Ca2+ made the cells spherical, and it nearly abolished cyclic AMP response as did lack of Mg2+.

Animals↗

Pseudohypoparathyroidism: a difficult diagnosis in early childhood.

We have studied one adult and three children with pseudohypoparathyroidism and observed that the physical character of short metacarpal bones is not evident in the first 4-5 years of life, that hypocalcaemia and hyperphosphataemia may be absent in the first years of life, but that the renal unresponsiveness to parathyroid hormone can still be demonstrated. Our data confirm earlier observation that in evaluating the renal responsiveness to parathyroid hormone, urinary cyclic AMP is a better parameter than urinary phosphorus. Thus in early childhood, it may be difficult to differentiate between a normal child, a child with pseudohypoparathyroidism and a child with pseudo-pseudohypoparathyroidism unless the renal parathyroid hormone responsiveness is studied.

Adult↗

Basal and hormone-induced urinary cyclic AMP in children with renal disorders.

The excretion of cyclic AMP in urine has been examined in normal children and in children with nephrogenic diabetes insipidus or moderate renal failure (predominantly defective concentrating ability) under basal conditions and in response to antidiuretic hormone (ADH) and parathyroid hormone (PTH). In contrast to other reported data, we could not confirm an ADH- and (PTH-unresponsiveness in hereditary, congenital nephrogenic diabetes insipidus, but our patients with structural renal disorders characterized by a defective urine concentrating ability did have reduced hormonal responses. It seems necessary to define nephrogenic diabetes insipidus very carefully, and until more data are collected, there appears to be no value in the measurement of urinary cyclic AMP level in the individual patient in the differential diagnosis of disorders due to renal concentrating defects.

Adolescent↗

Adenosine 3',5'-cyclic monophosphate in perfused rat hearts exposed to isoprenaline and dopamine.

Isoprenaline and dopamine increased cyclic AMP (cAMP) content and contractile activity of isolated perfused rat hearts. The changes of cAMP levels depended on the mode of drug administration. Isoprenaline (4 x 10(-10) mol) administered to the perfused heart as a relatively concentrated bolus, caused a substantial, rapid and transient increase of cAMP. Isoprenaline (2 x 10(-10) mol and 4 x 10(-10) mol) and dopamine (10(-7) mol) diluted in 40 ml of perfusate which was continuously recirculated through the heart, caused a gradual increase of cAMP content which approached an apparent steady state. cAMP accumulation occurred at isoprenaline concentrations above 10(-9) M and at dopamine concentrations above 10(-6) M. Both agents also increased cAMP labelling from 14C-adenine in the perfusate, probably indicating increased cAMP synthesis. Isoprenaline at 2 x 10(-8) M and 10(-7) M increased labelling more than content of cAMP. Isoprenaline and dopamine also increased phosphorylase a activity. An association between increased cAMP contents and increased contractile activity was revealed by both the time-response and the dose-response curves of hearts exposed to isoprenaline and dopamine. Since both agents stimulate adrenergic beta-receptors in cardiac muscle, the results are concordant with the hypothesis that cAMP is involved as a mediator of the inotropic response to adrenergic beta-stimulation.

Adenine↗

Role of cyclic adenosine 3',5'-monophosphate in the isoprenaline-induced relaxation of the oestrogen dominated rabbit uterus.

1. The role of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the relaxation produced by isoprenaline in muscle strips from the oestrogen dominated rabbit uterus has been investigated. 2. Isoprenaline 2 times 10- minus 8 M produced an inhibition of the mechanical activity but no increase in cyclic AMP. Isoprenaline 2 times 10- minus 6 M produced both inhibition of mechanical activity and increase in cyclic AMP. 3. The increase in cyclic AMP, but not the inhibition of mechanical activity, was blocked by propranolol 3.4 X 10-MINUS 6 M. 4. Dibutyryl-ccylic AMP produced a relaxation which mimicked that produced by isoprenaline, in that the longitudinal strips were more sensitive than the circular ones. 5. It is concluded that cyclic AMP may be a mediator of the beta-adrenergic effect in the oestrogen dominated rabbit myometrium. However, it seems not to be an obligatory link between stimulation of beta-adrenoceptors and relaxation. Other mechanisms may also exist.

Animals↗