Effect of calcium entry blockade on the actions of phenylephrine on the taenia of the guinea pig caecum.
The interaction between phenylephrine and calcium entry blockers was studied on the taenia of the guinea-pig caecum using the double sucrose gap method. Sustained hyperpolarization, relaxation and attenuation of evoked electrical and mechanical activity were induced by non-cumulative addition of phenylephrine (0.1 to 250 mumol.1-1) for 2 to 4 min. When the alpha 1-adrenoceptor agonist was applied for a prolonged period (20 to 60 min) the initial inhibitory response gradually disappeared both at room temperature and at 32 degrees C. The renewed action potentials were accompanied by a positive afterpotential. The initial hyperpolarization and its delayed recovery in course of the phenylephrine effect were significantly reduced in calcium-free medium containing EDTA (2 mmol.1-1), after pretreatment with nifedipine (0.1 to 1 mumol.1-1), verapamil (10 to 100 mumol.1-1) or procaine (0.5 to 2 mmol.1-1). In contrast sodium nitroprusside (10 to 100 mumol.1-1) which produced biphasic changes similar to those of phenylephrine, did not affect the initial and delayed phase of phenylephrine action. Ba2+(5 mmol.1-1) could substitute for Ca2+ in the generation of action potentials but could not substitute for Ca2+ in the mechanisms responsible for the initial and delayed recovery phase of phenylephrine effects. In the presence of La3+ and Mn2+ (0.5 to 3 mmol.1-1) the phenylephrine effects were reduced. In contrast, in the presence of extracellular Ca2+, pretreatment with Mg2+ (12 mmol.1-1) or Ba2+ (5 mmol.1-1) did not affect the action of phenylephrine. It is concluded that activation of alpha 1-adrenoceptors results in the release of Ca2+ from an intracellular store, which leads to the opening od TEA-sensitive potassium channels, causing the initial phase of alpha 1-adrenoceptor action. Ca2+ is loaded into this intracellular store by entering the cell through the potential sensitive calcium channels. Although the mechanisms responsible for the delayed phase could not be clarified, its dependence on the presence of the initial phase is apparent.
Rusko
J
J
Centre of Physiological Sciences, Slovak Academy of Sciences, Bratislava.
Bauer
V
V
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002432:Cecum / Q000187:drug effects; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology; D011343:Procaine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D009599:Nitroprusside; D010656:Phenylephrine; D011343:Procaine; D014700:Verapamil; D009543:Nifedipine; D011188:Potassium; D002118:Calcium