The expression of functional postsynaptic alpha2-adrenoceptors in the corpus cavernosum smooth muscle.
1. The purpose of this study was to determine if corpus cavernosum smooth muscle expresses functional postsynaptic alpha2-adrenoceptors (AR). 2. The alpha2-adrenoceptor agonist UK 14,304 elicited concentration-dependent contractions in rabbit corpus cavernosum smooth muscle (CCSM). The half-maximal response occurred at 0.32+/-0.03 microM and the maximum contraction at 10 microM UK 14,304. 3. Pretreatment of CCSM strips with selective alpha2-adrenoceptor antagonists, rauwolscine and RS-15385, produced rightward shifts in the dose-response curves to UK 14,304 (pA2 values 7.1 and 8.5, respectively). In contrast, these antagonists did not alter contraction induced by the alpha1-adrenoceptor agonist phenylephrine (PE) or oxymetazoline. UK 14,304-induced contractions were also inhibited by prazosin (pA2 = 9.08). 4. UK 14,304-induced contractions, unlike those to PE, were highly dependent on the presence of extracellular Ca2+. 5. [3H]-rauwolscine bound to CCSM membranes with high affinity (Kd = 1.5 nM). [3H]-rauwolscine binding was displaced by unlabelled rauwolscine, RS-15385, UK 14,304 and prazosin, but not by PE. 6. UK 14,304 inhibited forskolin and prostaglandin E1 (PGE1)-induced increases in intracellular cyclic AMP concentration in primary cultures of rabbit CCSM cells. 7. These results demonstrate that CCSM expresses Gi-coupled postsynaptic alpha2-adrenoceptors, and activation of these receptors causes contraction of trabecular smooth muscle.
Gupta
S
S
Department of Urology, Boston University School of Medicine, MA 02118, USA.
Moreland
R B
RB
Yang
S
S
Gallant
C M
CM
Goldstein
I
I
Traish
A
A
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D000068438:Brimonidine Tartrate; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism*; D010109:Oxymetazoline / Q000494:pharmacology; D010413:Penis / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D011869:Radioligand Assay; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D015290:Second Messenger Systems; D013569:Synapses / Q000378:metabolism*; D014316:Tritium; D015016:Yohimbine / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D014316:Tritium; D010656:Phenylephrine; D015016:Yohimbine; D000068438:Brimonidine Tartrate; D010109:Oxymetazoline; D000242:Cyclic AMP; D002118:Calcium; D011224:Prazosin