The role of alpha(1)-adrenoceptors and 5-HT(1A) receptors in the control of the micturition reflex in male anaesthetized rats. 2001

R K Conley, and T J Williams, and A P Ford, and A G Ramage
Department of Pharmacology, University College London, Royal Free Campus, Rowland Hill Street, Hampstead, London, NW3 2PF.

1. The effects of the alpha(1)-adrenoceptor antagonists doxazosin (0.1 -- 2 mg kg(-1)), RS-100329 (alpha(1A); 0.01 -- 1 mg kg(-1)), RS-513815 (Ro 151-3815, alpha(1B); 0.3 -- 3 mg kg(-1)) and BMY 7378 (alpha(1D); 0.1 -- 1 mg kg(-1)), the 5-HT(1A) receptor agonist, 8-OH-DPAT (0.03 -- 0.3 mg kg(-1)) and antagonist WAY-100635 (0.03 -- 0.3 mg kg(-1)) were investigated (i.v.) on the 'micturition reflex' in the urethane anaesthetized male rat. 2. Reflex-evoked urethra contractions were most sensitive to the inhibitory action of RS-100329, followed by doxazosin, BMY 7378 and WAY-100635 and then RS-513815. The maximum inhibition was 66, 63, 54, 46 and 22% at doses of 0.3, 0.5, 0.3, 0.3 and 3 mg kg(-1) respectively. 3. BMY 7378 and 8-OH-DPAT decreased, while WAY-100635 increased, the pressure threshold to induce bladder contraction. WAY-100635 (0.01 mg kg(-1)) blocked the effects of BMY 7378 (1 mg kg(-1)) on bladder pressure and volume threshold. 4. Doxazosin, RS-100329 and BMY 7378 had a similar potency in inducing a fall in arterial blood pressure while WAY-100635 only caused a fall at the highest dose. 5. Therefore, reflex-evoked urethral contraction involves the activation of alpha(1A/1D)-adrenoceptors, as BMY 7378 and RS-100329 are similarly potent in attenuating this effect. The ability of WAY-100635 to attenuate this contraction may suggest that 5-HT(1A) receptors are also involved. However, as this inhibition occurred at the highest dose of WAY-100635, which also caused a fall in arterial blood pressure; this effect is considered to be due to blockade of alpha(1)-adrenoceptors not 5-HT(1A) receptors. Nevertheless the initiation of the 'micturition reflex' involves the activation of 5-HT(1A) receptors.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008297 Male Males
D008991 Monitoring, Physiologic The continuous measurement of physiological processes, blood pressure, heart rate, renal output, reflexes, respiration, etc., in a patient or experimental animal; includes pharmacologic monitoring, the measurement of administered drugs or their metabolites in the blood, tissues, or urine. Patient Monitoring,Monitoring, Physiological,Physiologic Monitoring,Monitoring, Patient,Physiological Monitoring
D011985 Receptors, Serotonin Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. 5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D012018 Reflex An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord.
D001743 Urinary Bladder A musculomembranous sac along the URINARY TRACT. URINE flows from the KIDNEYS into the bladder via the ureters (URETER), and is held there until URINATION. Bladder,Bladder Detrusor Muscle,Detrusor Urinae,Bladder Detrusor Muscles,Bladder, Urinary,Detrusor Muscle, Bladder,Detrusor Muscles, Bladder
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002038 Bungarotoxins Neurotoxic proteins from the venom of the banded or Formosan krait (Bungarus multicinctus, an elapid snake). alpha-Bungarotoxin blocks nicotinic acetylcholine receptors and has been used to isolate and study them; beta- and gamma-bungarotoxins act presynaptically causing acetylcholine release and depletion. Both alpha and beta forms have been characterized, the alpha being similar to the large, long or Type II neurotoxins from other elapid venoms. alpha-Bungarotoxin,beta-Bungarotoxin,kappa-Bungarotoxin,alpha Bungarotoxin,beta Bungarotoxin,kappa Bungarotoxin
D006339 Heart Rate The number of times the HEART VENTRICLES contract per unit of time, usually per minute. Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse
D000317 Adrenergic alpha-Antagonists Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma. Adrenergic alpha-Receptor Blockaders,alpha-Adrenergic Blocking Agents,alpha-Adrenergic Receptor Blockaders,alpha-Blockers, Adrenergic,Adrenergic alpha-Blockers,alpha-Adrenergic Antagonists,alpha-Adrenergic Blockers,Adrenergic alpha Antagonists,Adrenergic alpha Blockers,Adrenergic alpha Receptor Blockaders,Agents, alpha-Adrenergic Blocking,Antagonists, alpha-Adrenergic,Blockaders, Adrenergic alpha-Receptor,Blockaders, alpha-Adrenergic Receptor,Blockers, alpha-Adrenergic,Blocking Agents, alpha-Adrenergic,Receptor Blockaders, alpha-Adrenergic,alpha Adrenergic Antagonists,alpha Adrenergic Blockers,alpha Adrenergic Blocking Agents,alpha Adrenergic Receptor Blockaders,alpha Blockers, Adrenergic,alpha-Antagonists, Adrenergic,alpha-Receptor Blockaders, Adrenergic

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