Receptor subtypes mediating renal actions of calcitonin gene-related peptide.
We previously reported that the renal arterial infusions of non-hypotensive doses of calcitonin gene-related peptide (CGRP) caused renal vasodilatation and increases in glomerular filtration rate at a low dose, but renal vasoconstriction, natriuresis and kaliuresis at a high dose. In the present study, we examined the effects of the specific CGRP1 receptor antagonist (CGRP-(8-37) (1 and 10 nmol/kg) and the putative CGRP receptor antagonist, [Tyr(0)]CGRP-(28-37)(3 and 30 nmol/kg), on the renal vascular and tubular effects of CGRP in inactin-anaesthetized Sprague-Dawley rats. Renal arterial infusion of single doses of CGRP (0.3-300 pmol/kg per min) did not significantly alter mean arterial pressure or heart rate. However, during the continuous renal arterial infusion of either CGRP-(8-37) or [Tyr(0)CGRP-(28-37) incompletely inhibited the vasoconstriction but did not inhibit diuresis, natriuresis and kaliuresis elicited by a high but non-hypotensive dose of CGRP. On the basis that CGRP-(8-37) is a competitive CGRP1 receptor antagonist, our results suggest: (1) the renal vascular effect of CGRP is completely mediated via the activation of CGRP1 receptors, (2) the renal tubular effects of CGRP are not mediated via CGRP1 receptors, and (3) [Tyr(0)]CGRP-(28-37) is a CGRP1 receptor antagonist with potency and efficacy less than those of CGRP-(8-37).
Elhawary
A M
AM
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Poon
J S
JS
Pang
C C
CC
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000502:physiology*; D012964:Sodium / Q000652:urine
D010446:Peptide Fragments; D018015:Receptors, Calcitonin Gene-Related Peptide; C058636:calcitonin gene-related peptide (8-37); D012964:Sodium; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium