title: Functional involvement of L-type calcium channels and cyclic nucleotide-dependent pathways in cadmium-induced myometrial relaxation in rats.
abstract: Modulation of myometrial spontaneity by cadmium (Cd) and its regulatory pathways was studied in rat uterus in the absence and presence of blockers of different signaling pathways. Isometric tension in myometrial strips, under a resting tension of 1 g, mounted in organ bath containing Ringer-Locke solution (RLS) continuously aerated with carbogen, was measured using data acquisition system-based physiograph and Lab Chart Pro V7.3.7 software. Mean integral tension was measured for 8 min. Cd (1 nM-0.1 mM) not only produced concentration-dependent inhibitory effect on rat myometrium but it (10 µM) also significantly ( p < 0.05) inhibited calcium chloride and BAY K-8644-induced myometrial contraction. Glybenclamide (10 µM), 4-aminopyridine (1 mM), and propranolol (10 µM) failed to significantly attenuate Cd-induced inhibitory responses, while L-NAME (0.1 mM), 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 25 µM), and 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22536; 1 µM) significantly ( p < 0.05) produced inhibitory effects on Cd-induced myometrial relaxation. Phenylephrine (1 nM-10 µM) and salbutamol (0.01 nM-0.1 µM)-induced relaxant effects on rat myometrium were significantly potentiated by 10 µM Cd. Thus based on the results of present functional study, it may be inferred that inhibitory effects of Cd on rat myometrium are mediated through blockade of L-type calcium channels and activation of NOS-NO-sGC and/or AC-cAMP pathways.
authors.affiliation: 1 Department of Pharmacology & Toxicology, Post Graduate Institute of Veterinary and Animal Sciences, Akola, MAFSU, Nagpur, Maharashtra, India.
authors.forename: V K
authors.initials: VK
authors.lastname: Saroj
authors.affiliation: 2 Department of Veterinary Pharmacology and Toxicology, Experimental Pharmacology Laboratory, College of Veterinary Science and Animal Husbandry, U.P. Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go-Anusandhan Sansthan, Mathura, India.
authors.forename: U P
authors.initials: UP
authors.lastname: Nakade
authors.affiliation: 2 Department of Veterinary Pharmacology and Toxicology, Experimental Pharmacology Laboratory, College of Veterinary Science and Animal Husbandry, U.P. Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go-Anusandhan Sansthan, Mathura, India.
authors.forename: A
authors.initials: A
authors.lastname: Sharma
authors.affiliation: 2 Department of Veterinary Pharmacology and Toxicology, Experimental Pharmacology Laboratory, College of Veterinary Science and Animal Husbandry, U.P. Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go-Anusandhan Sansthan, Mathura, India.
authors.forename: R S
authors.initials: RS
authors.lastname: Yadav
authors.affiliation: 1 Department of Pharmacology & Toxicology, Post Graduate Institute of Veterinary and Animal Sciences, Akola, MAFSU, Nagpur, Maharashtra, India.
authors.forename: S W
authors.initials: SW
authors.lastname: Hajare
authors.affiliation: 2 Department of Veterinary Pharmacology and Toxicology, Experimental Pharmacology Laboratory, College of Veterinary Science and Animal Husbandry, U.P. Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go-Anusandhan Sansthan, Mathura, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Garg
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020746:Calcium Channels, L-Type; D002104:Cadmium; D010656:Phenylephrine; D011433:Propranolol; D015761:4-Aminopyridine; D006152:Cyclic GMP; D005905:Glyburide
keywords: Cadmium; L-type calcium channel; adenylyl cyclase; guanylyl cyclase; rat myometrium