Abstract
Summary
The effect of dopamine (DOP), dopamine-receptor antagonist, and β-adrenergic receptor antagonist agents on simultaneously measured renin release (RR) and cyclic adenosine 3':5'-monophosphate (cAMP) content of renal cortical slices from sodium-deficient rats was studied in vitro. A DOP dose of 10-5 M significantly increased RR while a higher (10-3 M) dose significantly stimulated both RR and cAMP content in the slice preparation. Addition of the DOP-receptor blocker pimozide (PIMO) at 10-6 M effectively prevented stimulation of RR and tissue cAMP content by DOP. However, PIMO added alone also significantly decreased resting RR and tissue cAMP content levels. In subsequent experiments, the DOP-β-hydroxylase (DBH) enzyme inhibitor FLA-63 (10-4 M) was used in conjunction with the other agents to prevent conversion of DOP to norepinephrine (NE) in the tissue preparation. In the presence of FLA-63, 10-3 M DOP again significantly stimulated both RR and cAMP content as previously seen without FLA-63. Conversely, a previously inhibitory effect on RR was converted to significant stimulation by several PIMO doses in the presence of the DBH enzyme inhibitor. Tissue cAMP content appeared significantly inhibited by all PIMO doses added alone or together with 10-3 M DOP whether FLA-63 was present or not. FLA-63 was ineffective by itself. A 10-4 M dose of the β-adrenergic receptor blocker dl-propranolol (PROP), added together with 10-3 M DOP and FLA-63, significantly prevented the stimulatory effect of DOP on RR and tissue cAMP content. These data indicate that (i) DOP itself can directly stimulate RR from the renal juxtaglomerular cells, (ii) a direct stimulatory effect of DOP on RR is at least partially mediated by a β-adrenergic receptor mechanism involving intracellular cAMP changes, and (iii) further studies are needed before the possibility of the existence of dopamine-specific renal receptors mediating the action of DOP on RR can be properly evaluated.
The expert technical assistance of J. Cottrell, M. Kennedy, K. Kellner, G. Kristy, and J. Quero is gratefully acknowledged. The authors also wish to thank Dr. I. A. Reid, Department of Physiology, University of California Medical Center in San Francisco, for kindly supplying us with 24-hr nephrectomized dog plasma and angiotensin I antibody. Special thanks are also expressed to Dr. R. V. Gallo, Department of Physiology, University of California Medical Center in San Francisco, for his generous donation of pimozide.
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