Calcitonin gene-related peptide: effects on renal arteriolar tone and tubular cAMP levels.
The effects of calcitonin gene-related peptide (CGRP) and salmon calcitonin (SCT) on isolated afferent and efferent arteriolar tone and on adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in isolated tubules from rabbit kidney were compared. By themselves, CGRP and SCT had no effect on arteriole diameter. In norepinephrine-contracted afferent arterioles, CGRP, but not SCT, produced a concentration-dependent relaxation [50% maximal dose, (EC50) = 1.3 nM]. In contrast, neither CGRP nor SCT had any effect on efferent arterioles precontracted with norepinephrine or angiotensin II. CGRP, but not SCT, stimulated cAMP accumulation in glomeruli (EC50 = 0.5 nM). In tubules, CGRP increased cAMP levels only in SCT-responsive segments, e.g., cortical and medullary thick ascending limbs and distal convoluted tubules. In the medullary thick ascending limb, CGRP was approximately 500-fold less potent than SCT in stimulating cAMP accumulation with EC50s of 0.22 microM and 0.41 nM, respectively. The effect of maximum concentrations (1 microM) of CGRP and SCT on cAMP levels in the medullary thick ascending limb were not additive. The results suggest that there are specific CGRP receptors on afferent arterioles that produce relaxation and in glomeruli that are associated with an increase in cAMP production. In tubules, CGRP appears to be a weak agonist at the SCT receptor. We conclude that CGRP may play a role in the regulation of renal hemodynamics.
Edwards
R M
RM
Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, Pennsylvania 19406-0939.
Trizna
W
W
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002116:Calcitonin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D008138:Loop of Henle / Q000378:metabolism; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009994:Osmolar Concentration; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects*; D012474:Salmon
D002116:Calcitonin; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide