Role of intracellular calcium in the spermicidal action of 2',4'-dichlorobenzamil, a novel contact spermicide.
The Na+-Ca2+ exchanger and Ca2+-ATPase pumps reported to be present on the sperm membrane are responsible for maintaining the intracellular Ca2+ concentration that is involved in regulation of sperm function. We have investigated the role of intracellular Ca2+ in the presence of 2',4'-dichlorobenzamil hydrochloride (benzamil), a Na+-Ca2+ exchange inhibitor, on human sperm motility. The mechanism of the complementary spermicidal action produced by a combination of benzamil and propranolol on human spermatozoa has been investigated also. When administered alone benzamil and propranolol produced a dose- and time-dependent decrease in motility of sperm in ejaculated semen and spermatozoa separated from semen. A combination of benzamil and propranolol exhibited a complementary spermicidal action, thereby resulting in dose reduction of both drugs for obtaining total immotility within 1 min of administration. An increase in the intracellular Ca2+ level was found to contribute to the spermicidal activity. Inhibition of the Na+-Ca2+ exchange system on sperm membrane by benzamil and membrane stabilization by propranolol resulted in accumulation of Ca2+ inside the sperm cells. When the two drugs were used in combination the time required for the total loss of motility of spermatozoa was significantly reduced due to a similar mechanism of action of both drugs.
Patni
A K
AK
Department of Pharmaceutical Sciences & Drug Research, Punjabi University, Patiala, India.
Gupta
S
S
Sharma
A
A
Tiwary
A K
AK
Garg
S K
SK
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D012661:Semen / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013089:Spermatocidal Agents / Q000494:pharmacology*; D013094:Spermatozoa / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D013089:Spermatocidal Agents; D000584:Amiloride; C064515:2',4'-dichlorobenzamil amiloride; D011433:Propranolol; D002118:Calcium