title: Stimulation of alpha 2-adrenoreceptors blunts the phosphaturic response to parathyroid hormone.
abstract: Acute renal denervation is phosphaturic and enhances the phosphaturic response to parathyroid hormone (PTH). Stimulation of alpha-adrenoreceptors inhibits the renal accumulation of 3,5-cyclic adenosine monophosphate (cAMP) in response to PTH. However, the effect of this blunted cAMP response by stimulation of alpha-adrenoreceptors on the phosphaturic response to PTH is not well understood. Therefore, the effect of alpha-adrenergic stimulation on the phosphaturic response to PTH was studied by infusion of PTH in the presence and absence of epinephrine plus propranolol. Sprague-Dawley rats were acutely thyroparathyroidectomized, and the left kidney was denervated. Stimulation of alpha-adrenoreceptors significantly blunted the phosphaturic response to PTH, decreasing the change in fractional excretion of phosphate (delta FEp) (21.2% +/- 1.3%, n = 8), as compared with the response to PTH alone (FEp, 30.0% +/- 2.4%, n = 7). In subsequent studies, yohimbine (an alpha 2-adrenoreceptor antagonist) or prazosin (an alpha 1-antagonist) were infused to dissociate alpha 1 from alpha 2-adrenoreceptor activity. Coadministration of yohimbine tended to restore the blunted phosphaturic response to PTH induced by alpha-adrenergic stimulation (delta FEp, 25.8% +/- 2.4%, n = 9), whereas addition of prazosin did not affect the blunted response (delta FEp, 16.1% +/- 4.5%, n = 7). We conclude that stimulation of alpha-adrenoreceptors blunts the phosphaturic response to PTH, most likely due to enhanced alpha 2-adrenoreceptor activity.
authors.affiliation: Department of Physiology, Mayo Clinic and Foundation, Rochester, MN 55905.
authors.forename: J
authors.initials: J
authors.lastname: Isaac
authors.forename: T J
authors.initials: TJ
authors.lastname: Berndt
authors.forename: F G
authors.initials: FG
authors.lastname: Knox
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D016105:Parathyroidectomy; D010710:Phosphates / Q000097:blood / Q000652:urine*; D011224:Prazosin / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013965:Thyroidectomy; D015016:Yohimbine / Q000494:pharmacology*
chemical_list: D010281:Parathyroid Hormone; D010710:Phosphates; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D011433:Propranolol; D000242:Cyclic AMP; D011224:Prazosin; D004837:Epinephrine