title: Functional involvement of protein kinase C, Rho-kinase and TRPC3 decreases while PLC increases with advancement of pregnancy in mediating oxytocin-induced myometrial contractions in water buffaloes (Bubalus bubalis).
abstract: Present study unravels the involvement of different calcium signaling pathways in oxytocin-induced contractions in myometrium of non-pregnant and pregnant buffaloes during early and mid-pregnancy stages. Uteri of pregnant animals were more sensitive than of non-pregnant buffaloes. Phasic contractions and frequency of contraction significantly increased with advancement of pregnancy, while tonic contractions non-significantly and amplitude significantly decreased from six months pregnancy onward. Oxytocin produced concentration-dependent-contraction on isolated myometrial strips of pregnant and non-pregnant buffaloes and the dose response curves (DRCs) of oxytocin were significantly (P < 0.05) shifted to right in the presence of nifedipine (1 μM), in Ca2+-free Ringer Locke solution (RLS), ruthenium red (30 μM), ruthenium red + nifedipine, cyclopiazonic acid (CPA; Ca2+free RLS as well as RLS), CPA (10 μM)+nifedipine, U-73122 (1 μM) + nifedipine and SKF96365 (25 μM) on uteri of non-pregnant and pregnant (early and mid) animals. The DRCs were also significantly shifted towards right in the presence of Y-27632 (10 μM), GF109203X (5 μM) and Pyr3 (10 μM) on uteri of non-pregnant and early pregnancy stage buffaloes while only in the presence of U-73122 (1 μM) on uteri of mid-pregnancy stage buffaloes. Our finding suggest that and L-type Ca2+channels, IP3-RyR-gated, and store-operated calcium channels including transient receptor potential channel (TRPC) pathways play significant role in mediating oxytocin-induced contractions in myometrium of pregnant and non-pregnant buffaloes. SERCA plays major role only during early-pregnancy while functional role of protein kinase C (PKC), Rho-kinase and TRPC3 pathways decreased and role of G-protein coupled receptor-phospholipase C (GPCR-PLC) pathway increased with advancement of pregnancy.
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Sciences and Animal Husbandry, UP Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Gau Anusandhan Sansthan, Mathura, U.P. 281 001, India.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Sciences and Animal Husbandry, UP Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Gau Anusandhan Sansthan, Mathura, U.P. 281 001, India.
authors.forename: Udayraj P
authors.initials: UP
authors.lastname: Nakade
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Sciences and Animal Husbandry, UP Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Gau Anusandhan Sansthan, Mathura, U.P. 281 001, India.
authors.forename: Soumen
authors.initials: S
authors.lastname: Choudhury
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Sciences and Animal Husbandry, UP Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Gau Anusandhan Sansthan, Mathura, U.P. 281 001, India. Electronic address: profsatish@gmail.com.
authors.forename: Satish Kumar
authors.initials: SK
authors.lastname: Garg
mesh_terms: D000818:Animals; D002020:Buffaloes / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D007093:Imidazoles / Q000494:pharmacology; D007202:Indicators and Reagents / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology*; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007202:Indicators and Reagents; D011720:Pyrazoles; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D014665:Vasodilator Agents; C559943:ethyl-1-(4-(2*3*3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate; D012430:Ruthenium Red; D010121:Oxytocin; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine
keywords: Buffalo myometrium; Oxytocin; PKC; Phospholipase-C; Rho-kinase; Store-operated Ca(2+) channel/transient receptor potential channel