title: A Ca(2+)-sensing receptor modulates shark rectal gland function.
abstract: The elasmobranch Squalus acanthias controls plasma osmolality and extracellular fluid volume by secreting a hypertonic fluid from its rectal gland. Because we found a correlation between extracellular Ca(2+) concentration and changes in cytosolic Ca(2+) ([Ca(2+)](i)), we sought the possible presence of a calcium-sensing receptor in rectal gland artery and tubules. Cytosolic Ca(2+) of both tissues responded to the addition of external Ca(2+) (0.8-5.3 mmol l(-1)) in a linear fashion. Spermine, Gd(3+) and Ni(2+), known agonists of the calcium-sensing receptor, increased [Ca(2+)](i). To assess the participation of inositol triphosphate (IP(3)) generation, sarcoplasmic/endoplasmic reticulum (SR/ER) Ca(2+) depletion, and activation of store-operated Ca(2+) entry, we utilized thapsigargin and ryanodine to deplete Ca(2+) SR/ER stores and the inhibitory reagents TMB-8 and 2-APB to block IP(3) receptors. In each case, these agents inhibited the [Ca(2+)](i) response to agonist stimulation by approximately 50 %. Blockade of L-channels with nifedipine had no significant effect. Increases in ionic strength are known to inhibit the calcium-sensing receptor. We postulate that the CaSR stimulates Ca(2+)-mediated constriction of the rectal gland artery and diminishes cyclic AMP-mediated salt secretion in rectal gland tubules during non-feeding conditions. When the shark ingests sea water and fish, an increase in blood and interstitial fluid ionic strength inhibits the activity of the calcium-sensing receptor, relaxing the rectal gland artery and permitting salt secretion by the rectal gland tubules.
authors.affiliation: Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. sfellner@med.unc.edu
authors.forename: Susan K
authors.initials: SK
authors.lastname: Fellner
authors.forename: Laurel
authors.initials: L
authors.lastname: Parker
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004284:Dogfish / Q000033:anatomy & histology / Q000502:physiology*; D005260:Female; D005682:Gadolinium / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009532:Nickel / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012433:Ryanodine / Q000494:pharmacology; D012491:Salt Gland / Q000187:drug effects / Q000502:physiology; D013096:Spermine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D001896:Boron Compounds; D002121:Calcium Channel Blockers; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D012433:Ryanodine; D013096:Spermine; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D019284:Thapsigargin; D009532:Nickel; D005682:Gadolinium; C109986:2-aminoethoxydiphenyl borate; D009543:Nifedipine; D002118:Calcium